@article{chung_zhang_collins_sper_gleason_simpson_koh_sommer_flowers_petters_et al._2018, title={High mobility group A2 (HMGA2) deficiency in pigs leads to dwarfism, abnormal fetal resource allocation, and cryptorchidism}, volume={115}, ISSN={0027-8424 1091-6490}, url={http://dx.doi.org/10.1073/pnas.1721630115}, DOI={10.1073/pnas.1721630115}, abstractNote={Significance}, number={21}, journal={Proceedings of the National Academy of Sciences}, publisher={Proceedings of the National Academy of Sciences}, author={Chung, Jaewook and Zhang, Xia and Collins, Bruce and Sper, Renan B. and Gleason, Katherine and Simpson, Sean and Koh, Sehwon and Sommer, Jeffrey and Flowers, William L. and Petters, Robert M. and et al.}, year={2018}, month={May}, pages={5420–5425} } @article{jeong_nelson_niedziela_dickey_2016, title={Effect of Plant Species, Fertilizer Acidity/Basicity, and Fertilizer Concentration on pH of Soilless Root Substrate}, volume={51}, ISSN={["2327-9834"]}, DOI={10.21273/hortsci11237-16}, abstractNote={The objective of this study was to determine how plant species, fertilizer potential acidity/basicity rating (PABR), and fertilizer concentration affect root substrate pH. Three experiments were conducted. In the first experiment, 13 herbaceous species were grown in a root substrate of three sphagnum peatmoss: one perlite (v/v) with deionized water and a neutral fertilizer (NF) with a PABR of 0 for 78 days to determine species relationships to substrate pH. The decrease in substrate pH ranged from 0.14 to 2.45 units, depending on species. In the second experiment, four of the 13 species from the previous trial representing the range of pH suppression were grown under similar growth conditions as the first experiment for 70 days. Substrate pH was lowered in the range of 0.47 to 2.72 units. In the third experiment, three fertilizers with PABRs of 150 kg·t−1 CaCO3 equivalent alkalinity, 0 neutral, and 193 kg·t−1 CaCO3 equivalent acidity were applied in a factorial design at 100 and 200 mg·L−1 N at each irrigation to kalanchoe (the species with the greatest pH suppression from the previous experiments) for 56 days. When applied at the lower fertilizer rate (100 mg·L−1 N), the PABRs resulted in the final substrate pH levels of 4.68, 5.60, and 6.11 for the acidic fertilizer (AF), NF, and basic fertilizer (BF), respectively. At the high fertilizer rate (200 mg·L−1 N), substrate pH declined continuously to 3.97, 4.03, and 4.92 for the AF, NF, and BF, respectively. Expression of PABR depended on the balance between the abiotic (chemical) effect of the fertilizers vs. the biotic (physiological) effects of the fertilizers on microbes and plants. The PABR was best expressed when the fertilizer supply was just adequate or lower indicating a closer connection to the biotic effect.}, number={12}, journal={HORTSCIENCE}, author={Jeong, Ka Yeon and Nelson, Paul V. and Niedziela, Carl E., Jr. and Dickey, David A.}, year={2016}, month={Dec}, pages={1596–1601} } @article{sommer_chavali_simpson_ayyagari_petters_2012, title={Cloning, characterization, and expression analysis of the pig (Sus scrofa) C1q tumor necrosis factor-related protein-5 gene}, volume={18}, number={12-14}, journal={Molecular Vision}, author={Sommer, J. R. and Chavali, V. R. M. and Simpson, S. G. and Ayyagari, R. and Petters, R. M.}, year={2012}, pages={92–102} } @article{klassen_kiilgaard_warfvinge_samuel_prather_wong_petters_cour_young_2012, title={Photoreceptor Differentiation following Transplantation of Allogeneic Retinal Progenitor Cells to the Dystrophic Rhodopsin Pro347Leu Transgenic Pig}, volume={2012}, ISSN={["1687-9678"]}, DOI={10.1155/2012/939801}, abstractNote={Purpose. Transplantation of stem, progenitor, or precursor cells has resulted in photoreceptor replacement and evidence of functional efficacy in rodent models of retinal degeneration. Ongoing work has been directed toward the replication of these results in a large animal model, namely, the pig.Methods. Retinal progenitor cells were derived from the neural retina of GFP-transgenic pigs and transplanted to the subretinal space of rhodopsin Pro347Leu-transgenic allorecipients, in the early stage of the degeneration and the absence of immune suppression.Results. Results confirm the survival of allogeneic porcine RPCs without immune suppression in the setting of photoreceptor dystrophy. The expression of multiple photoreceptor markers by grafted cells included the rod outer segment-specific marker ROM-1. Further evidence of photoreceptor differentiation included the presence of numerous photoreceptor rosettes within GFP-positive grafts, indicative of the development of cellular polarity and self-assembly into rudiments of outer retinal tissue.Conclusion. Together, these data support the tolerance of RPCs as allografts and demonstrate the high level of rod photoreceptor development that can be obtained from cultured RPCs following transplantation. Strategies for further progress in this area, together with possible functional implications, are discussed.}, journal={STEM CELLS INTERNATIONAL}, author={Klassen, H. and Kiilgaard, J. F. and Warfvinge, K. and Samuel, M. S. and Prather, R. S. and Wong, F. and Petters, R. M. and Cour, M. and Young, M. J.}, year={2012} } @article{sommer_jackson_simpson_collins_piedrahita_petters_2012, title={Transgenic Stra8-EYFP pigs: a model for developing male germ cell technologies}, volume={21}, ISSN={["0962-8819"]}, DOI={10.1007/s11248-011-9542-6}, abstractNote={The male germ line in mammals is composed of self-renewing cells, spermatogonia, the meiotic spermatocytes and spermiogenic spermatids. Identification of these cell stages in vitro has been problematic. Transgenic animals expressing a marker gene with a promoter specific to certain cell stages in the testis would be a useful approach to identifying these cells in a viable state. Towards this end, we have produced transgenic pigs expressing mitochondrial localized enhanced yellow fluorescent protein (EYFP-mito) under control of the germ cell specific Stimulated by Retinoic Acid 8 (Stra8) promoter. Stra8 has been shown to be expressed in pre-meiotic germ cells of mice. Twelve clones harboring the Stra8-EYFP-mito transgene were produced. Analysis by Western blot indicated that expression of the transgene was limited to testicular tissue in the transgenic pigs. Single cells and seminiferous tubules were cultured in vitro and subsequently examined with epifluorescent microscopy. Expression of EYFP was noted in cells cultured for up to 5 days. Both EYFP-mito and STRA8 antibodies were shown to bind and co-localize in seminiferous tubule cells in whole mounts and in histological sections. EYFP-mito in the transgenic pigs co-localized with the endogenous stem cell marker, NANOG. Expression of the Stra8-EYFP transgene in spermatogenic cells indicates that these pigs will be useful by providing labelled cells for use in such technologies such as germ cell transplantation and in vitro spermatogenic studies.}, number={2}, journal={TRANSGENIC RESEARCH}, author={Sommer, Jeffrey R. and Jackson, Lauren R. and Simpson, Sean G. and Collins, Edwin B. and Piedrahita, Jorge A. and Petters, Robert M.}, year={2012}, month={Apr}, pages={383–392} } @article{sommer_wong_petters_2011, title={Phenotypic stability of Pro347Leu rhodopsin transgenic pigs as indicated by photoreceptor cell degeneration}, volume={20}, ISSN={["0962-8819"]}, DOI={10.1007/s11248-011-9491-0}, abstractNote={Rhodopsin (Pro347Leu) transgenic pigs are recognized to be an excellent model for the human disease, retinitis pigmentosa. First published in 1997, the rhodopsin transgenic pigs have been maintained since that time at North Carolina State University by outcrossing hemizygous boars to unrelated sows. Nine generations of outcrossing have been completed. Since the genetic background of these pigs has undoubtedly changed, the question of the current phenotype of the transgenic pigs is relevant for their future use. Age-matched transgenic and non-transgenic eyes were submitted for histological analysis using hematoxylin and eosin staining. Even by 2 weeks of age, significant thinning of the outer nuclear layer of photoreceptors was observed. For ages 3 and 4 weeks, thinning was noted similar to that of 2 weeks of age. By 6 weeks of age outer nuclear layer thinning was greater than that of earlier age. At 11 weeks of age, most of the rods have degenerated leaving only a few layers of cones. In all, the phenotype, based on assessment of photoreceptor degeneration, is similar to that of the first description of the transgenic animals. As such the Pro347Leu rhodopsin transgenic pigs have exhibited phenotypic stability through generations of outcrossing and can be used confidently in future studies of the type of retinal degeneration seen with retinitis pigmentosa.}, number={6}, journal={TRANSGENIC RESEARCH}, author={Sommer, Jeffrey R. and Wong, Fulton and Petters, Robert M.}, year={2011}, month={Dec}, pages={1391–1395} } @article{sommer_estrada_collins_bedell_alexander_yang_hughes_mir_gilger_grob_et al._2011, title={Production of ELOVL4 transgenic pigs: a large animal model for Stargardt-like macular degeneration}, volume={95}, ISSN={0007-1161}, url={http://dx.doi.org/10.1136/bjophthalmol-2011-300417}, DOI={10.1136/bjophthalmol-2011-300417}, abstractNote={Background Truncation mutations in the elongation of very long chain fatty acids-4 (AF277094, MIM #605512) (ELOVL4) gene cause Stargardt-like macular dystrophy type 3 (STGD3). Mice expressing truncated ELOVL4 develop rapid retinal degeneration, but are poor STGD3 models since mice lack a macula. Photoreceptor topography in the pig retina is more similar to that in humans as it includes the cone rich, macula-like area centralis. The authors generated transgenic pigs expressing human disease-causing ELOVL4 mutations to better model the pathobiology of this macular disease. Methods Pronuclear DNA microinjection and somatic cell nuclear transfer were used to produce transgenic pigs for two different ELOVL4 mutations: the 5 base pair deletion (5 bpdel) and the 270 stop mutation (Y270terEYFP). Retinal transgene expression, morphology and electrophysiology were examined. Results The authors obtained four lines of Y270terEYFP and one line of 5 bpdel transgenic animals. Direct fluorescence microscopy indicated that the Y270terEYFP protein is expressed in photoreceptors and mislocalised within the cell. Immunohistochemical examination of transgenic pigs showed photoreceptor loss and disorganised inner and outer segments. Electroretinography demonstrated diminished responses in both transgenic models. Conclusions These transgenic pigs provide unique animal models for examining macular degeneration and STGD3 pathogenesis.}, number={12}, journal={British Journal of Ophthalmology}, publisher={BMJ}, author={Sommer, J. R. and Estrada, J. L. and Collins, E. B. and Bedell, M. and Alexander, C. A. and Yang, Z. and Hughes, G. and Mir, B. and Gilger, B. C. and Grob, S. and et al.}, year={2011}, month={Aug}, pages={1749–1754} } @article{chavali_sommer_petters_ayyagari_2010, title={Identification of a Promoter for the Human C1q-Tumor Necrosis Factor-Related Protein-5 Gene Associated with Late-Onset Retinal Degeneration}, volume={51}, ISSN={["1552-5783"]}, DOI={10.1167/iovs.10-5543}, abstractNote={PURPOSE The Complement-1q tumor necrosis factor-related protein 5 (C1QTNF5/CTRP5) gene is located in the 3' untranslated region of the Membrane Frizzled Related Protein (MFRP) gene, and these two genes are reported to be dicistronic. The authors examined the 5' upstream sequence of CTRP5 for the presence of a promoter regulating the expression of this gene. METHODS The sequence upstream of the translational start site of human CTRP5 (hCTRP5) was analyzed by Promoter Inspector software. A series of plasmids containing segments of hCTRP5 putative promoter sequence (-29 bp to -3.6 kb) upstream of the luciferase gene were generated. Cells were transiently transfected with these plasmids, and luciferase activity was measured. 5' RACE analysis was performed to determine the functional transcription start site. V5 tagged-pig CTRP5 (pCTRP5) gene, cloned downstream of the hCTRP5 putative promoter, was expressed in a human retinal cell line (ARPE-19) and a Chinese hamster ovary cell line (CHO-K1) to study the functionality of the putative promoter. RESULTS Bioinformatic analysis identified a putative promoter region between nt -1322 and +1 sequence of hCTRP5. 5' RACE analysis revealed the presence of the transcriptional start site (TSS) at 62 bp upstream of the start codon in the CTRP5. The 1.3-kb sequence of the hCTRP5 predicted promoter produced higher levels of luciferase activity, indicating the strength of the cloned CTRP5 promoter. The promoter sequence between nt -1322 bp to -29 bp upstream of the first ATG of CTRP5 was found to be essential for this promoter activity. The predicted hCTRP5 promoter was found to control the expression of V5-tagged pCTRP5 and nuclear GFP, indicating that the promoter was functional. CONCLUSIONS This study revealed the presence of a functional promoter for the CTRP5 gene located 5' of its start site. Understanding the regulation of CTRP5 gene transcription may provide insights into the possible role of CTRP5 in the retina and the pathology underlying late-onset retinal degeneration caused by mutations in this gene. In addition, these studies will determine whether CTRP5 and MFRP are functionally dicistronic.}, number={11}, journal={INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE}, author={Chavali, Venkata R. M. and Sommer, Jeffrey R. and Petters, Robert M. and Ayyagari, Radha}, year={2010}, month={Nov}, pages={5499–5507} } @article{ng_chan_chu_to_gilger_petters_wong_2008, title={Multifocal Electroretinogram in Rhodopsin P347L Transgenic Pigs}, volume={49}, ISSN={1552-5783}, url={http://dx.doi.org/10.1167/iovs.07-1159}, DOI={10.1167/iovs.07-1159}, abstractNote={PURPOSE Neural ectopic rewiring in retinal degeneration such as retinitis pigmentosa (RP) may form functional synapses between cones and rod bipolar cells that cause atypical signal processing. In this study, the multifocal electroretinograms (mfERGs) of a large animal model of RP, the rhodopsin P347L transgenic (Tg) pig, were measured to examine the sources and nature of altered signal processing. METHODS mfERG responses from a 6-week-old Tg pig were recorded before and after sequential application of tetrodotoxin (TTX), N-methyl-D-aspartate (NMDA), 2-amino-4-phosphonobutyric acid (APB), and cis-2,3-piperidinedicarboylic acid (PDA), to identify contributions to the retinal signal from inner retinal neurons, the ON-pathway, the OFF-pathway, and photoreceptors. The mfERG response contributions from different retinal components of in the Tg eyes were estimated and compared with control data from eyes of age-matched wild-type (WT) pigs. RESULTS There was a prominent difference in the estimates of the inner retinal response and ON-bipolar cell pathway contribution between the Tg and WT mfERG responses. In particular, the early components of the inner retinal contribution were obviously altered in the Tg mfERG. The inner retinal components at approximately 24 and 40 ms appeared to be inverted. Differences in the estimates of OFF-bipolar cell pathway contributions were minimal. There was no change in cone cell responses in the Tg mfERG. CONCLUSIONS In Tg retinas, ectopic synapses formed between cones and rod bipolar cells probably altered signal processing of the ON-bipolar cell pathway. In response to the altered visual signal input from the outer retina, signal processing in inner retinal neurons was also modified.}, number={5}, journal={Investigative Opthalmology & Visual Science}, publisher={Association for Research in Vision and Ophthalmology (ARVO)}, author={Ng, Yiu-fai and Chan, Henry H. L. and Chu, Patrick H. W. and To, Chi-ho and Gilger, Brian C. and Petters, Robert M. and Wong, Fulton}, year={2008}, month={May}, pages={2208} } @article{estrada_collins_york_bischoff_sommer_tsai_petters_piedrahita_2008, title={Successful cloning of the Yucatan minipig using commercial/occidental breeds as oocyte donors and embryo recipients}, volume={10}, ISSN={["1536-2302"]}, DOI={10.1089/clo.2008.0005}, abstractNote={The widespread application of porcine SCNT to biomedical research is being hampered by the large adult size (300-600 lbs) of the commercial breeds commonly used for SCNT. The Yucatan minipig, in contrast, has an adult weight of 140-150 lbs and a long history of utility in biomedical research. In order to combine the wide availability of commercial swine with the biomedical value of the Yucatan minipig, we utilized SCNT using the Yucatan as nuclear donors and commercial swine as both oocyte donors and recipients. Of six recipient gilts receiving 631 SCNT embryos, three went to term and delivered seven piglets, four of which survived to adulthood. Additionally, we obtained fetal fibroblasts from a cloned Yucatan and used them for a second round of SCNT. Of three recipients receiving 315 reconstructed embryos, one went to term and delivered three piglets, one of which survived to adulthood. Both microsatellite and D-loop sequence analysis confirmed that all of the piglets generated were nuclear-mitochondrial hybrids carrying Yucatan nuclear DNA and commercial breed mitochondrial DNA. This report shows that it is possible to produce viable Yucatan SCNT clones and opens up the possibility of developing valuable biomedical models in this porcine breed.}, number={2}, journal={CLONING AND STEM CELLS}, author={Estrada, Jose L. and Collins, Bruce and York, Abby and Bischoff, Steve and Sommer, Jeff and Tsai, Shengdar and Petters, Robert M. and Piedrahita, Jorge A.}, year={2008}, month={Jun}, pages={287–296} } @article{ghosh_engelsberg_english_petters_2007, title={Long-term neuroretinal full-thickness transplants in a large animal model of severe retinitis pigmentosa}, volume={245}, ISSN={["1435-702X"]}, DOI={10.1007/s00417-006-0437-9}, abstractNote={The purpose of this study was to explore neuroretinal transplantation in a large animal model of severe retinitis pigmentosa and to establish graft development, long-term survival, graft-host integration, and effects on the host retina. Rhodopsin transgenic pigs, aged 6 months, received in one eye a fetal full-thickness neuroretinal sheet in the subretinal space by means of vitrectomy and retinotomy. Six months postoperatively, eyes were studied in the light microscope and with immunohistochemical markers. Full-field electroretinography (ERG) was performed at 4 and 6 months. Laminated grafts with well-organized photoreceptors, rod bipolar cells, and Müller cells were found in five of six eyes. Neuronal connections between graft and host retina were not seen. In the five eyes containing a graft, the number of surviving rods in the host retina was significantly higher compared with unoperated eyes. The ERG did not reveal any significant difference in b-wave amplitude between operated and control eyes, but the cone-derived response in operated eyes increased significantly from 4 to 6 months while the rod response in control eyes decreased significantly. Fetal full-thickness neuroretina can be transplanted safely to an eye with severe retinal degeneration. In their major part, the transplants develop a normal laminated morphology and survive for at least 6 months. Graft and host retinal neurons do not form connections. Retinal function in the host is reduced initially by the surgical trauma, but the presence of a well-laminated graft counteracts this effect and rescues rods from degeneration.}, number={6}, journal={GRAEFES ARCHIVE FOR CLINICAL AND EXPERIMENTAL OPHTHALMOLOGY}, author={Ghosh, Fredrik and Engelsberg, Karl and English, Robert V. and Petters, Robert M.}, year={2007}, month={Jun}, pages={835–846} } @article{estrada_sommer_collins_mir_martin_york_petters_piedrahita_2007, title={Swine generated by somatic cell nuclear transfer have increased incidence of intrauterine growth restriction (IUGR)}, volume={9}, ISSN={["1536-2302"]}, DOI={10.1089/clo.2006.0079}, abstractNote={While somatic cell nuclear transfer (SCNT) has been successful in several species, many pregnancies are lost and anomalies are found in fetal and perinatal stages. In this study SCNT and artificial inseminations (AI) populations were compared for litter size, average birth weight, piglets alive at birth, stillborn, mummies, dead at the first week, intrauterine growth restriction (IUGR) and large for gestational age (LGA). Twenty-three SCNT litters (143 individuals) were compared to 112 AI litters (1300 individuals). Litter size average was 11.5 for AI and 6.2 for SCNT. Litter weight and average birth weight adjusted by litter size were significantly (p < 0.05) higher in AI than in SCNT litters. The SCNT population had a significant (p < 0.01) increase in the number of IUGRs per litter with LSmeans 7.2 +/- 1.4 versus 19.4 +/- 3.5 and means 8.0 +/- 10.8 versus 15.5 +/- 24.5 for AI and SCNT, respectively. Additionally, there was a trend for higher postnatal mortality and stillbirths in the SCNT population. These findings demonstrate that there are some differences between SCNT-derived and AI litters. SCNT-derived pigs are excellent models to study epigenetic factors and genes involved in IUGRs, and to develop effective means to improve fetal growth in humans and animals.}, number={2}, journal={CLONING AND STEM CELLS}, author={Estrada, Jose and Sommer, Jeffrey and Collins, Bruce and Mir, Bashir and Martin, Amy and York, Abby and Petters, Robert M. and Piedrahita, Jorge A.}, year={2007}, pages={229–236} } @article{sommer_collins_estrada_petters_2007, title={Synchronization and superovulation of mature cycling gilts for the collection of pronuclear stage embryos}, volume={100}, ISSN={["1873-2232"]}, DOI={10.1016/j.anireprosci.2006.10.010}, abstractNote={An efficient protocol was developed to synchronize and superovulate mature pigs for the collection of pronuclear stage embryos suitable for DNA microinjection. A timed and coordinated regimen of Lutalyse, PG600 and Chorulon along with daily checking for estrus allowed synchronization of groups of gilts having estrous cycles at regular intervals. Pigs 10-16 days after the beginning of standing estrus have been successfully synchronized into estrus using this protocol. A standard dose of each drug was used independent of size or age of the animal. One protocol averaged 38.9 ovulations and 31.1 one-cell embryos recovered per animal.}, number={3-4}, journal={ANIMAL REPRODUCTION SCIENCE}, author={Sommer, Jeffrey R. and Collins, E. Bruce and Estrada, Jose L. and Petters, Robert M.}, year={2007}, month={Aug}, pages={402–410} } @article{sommer_aiderson_laible_petters_2006, title={Reporter system for the detection of in vivo gene conversion - Changing colors from blue to green using GFP variants}, volume={33}, ISSN={["1559-0305"]}, DOI={10.1385/MB:33:2:115}, abstractNote={We have devised a system for the study of in vivo gene correction based on the detection of color variants of the green fluorescent protein (GFP) from the jellyfish Aequorea victoria. The intensity and spectra of the fluorescence emitted by the blue (BFP) and red-shifted (EGFP) variants of GFP differ from each other. We modified one nucleotide from an EGFP expression vector that we predicted would yield a blue variant (TAC-CAC, Tyr(66)-His(66)). Cells that were either transiently or stably transfected with the reporter system were used to test the functionality and feasibility of the detection of in vivo gene correction. A thio-protected single-stranded oligonucleotide designed to convert the genotype of the blue variant to that of the EGFP variant by the correction of a single base pair was delivered to the reporter cells using a variety of methodologies and strategies.Conversion events were easily observed using fluorescent microscopy because of the enhanced emission intensity and different spectra of the EGFP variant.}, number={2}, journal={MOLECULAR BIOTECHNOLOGY}, author={Sommer, Jeffrey R. and Aiderson, On and Laible, Goetz and Petters, Robert M.}, year={2006}, month={Jun}, pages={115–121} } @article{kraft_allen_petters_hao_peng_wong_2005, title={Altered light responses of single rod photoreceptors in transgenic pigs expressing P347L or P347S rhodopsin}, volume={11}, number={142}, journal={Molecular Vision}, author={Kraft, T. W. and Allen, D. E. and Petters, R. M. and Hao, Y. and Peng, Y. W. and Wong, F.}, year={2005}, pages={1246–1256} } @article{su_wu_sommer_gore_petters_miller_2005, title={Conditional induction of ovulation in mice}, volume={73}, ISSN={["1529-7268"]}, DOI={10.1095/biolreprod.104.039164}, abstractNote={Abstract Follicle-stimulating hormone controls the maturation of mammalian ovarian follicles. In excess, it can increase ovulation (egg production). Reported here is a transgenic doxycycline-activated switch, tested in mice, that produced more FSHB subunit (therefore more FSH) and increased ovulation by the simple feeding of doxycycline (Dox). The transgenic switch was expressed selectively in pituitary gonadotropes and was designed to enhance normal expression of FSH when exposed to Dox, but to be regulated by all the hormones that normally control FSH production in vivo. Feeding maximally effective levels of Dox increased overall mRNA for FSHB and serum FSH by over half in males, and Dox treatment more than doubled the normal ovulation rate of female mice for up to 10 reproductive cycles. Lower levels of Dox increased the number of developing embryos by 30%. Ovarian structure and function appeared normal. In summary, gene switch technology and normal FSH regulation were combined to effectively enhance ovulation in mice. Theoretically, the same strategy can be used with any genetic switch to increase ovulation (or any highly conserved physiology) in any mammal.}, number={4}, journal={BIOLOGY OF REPRODUCTION}, author={Su, P and Wu, JC and Sommer, JR and Gore, AJ and Petters, RM and Miller, WL}, year={2005}, month={Oct}, pages={681–687} } @article{shen_yang_dong_petters_peng_wong_campochiaro_2005, title={Oxidative damage is a potential cause of cone cell death in retinitis pigmentosa}, volume={203}, ISSN={["1097-4652"]}, DOI={10.1002/jcp.20346}, abstractNote={Abstract}, number={3}, journal={JOURNAL OF CELLULAR PHYSIOLOGY}, author={Shen, JK and Yang, XR and Dong, AL and Petters, RM and Peng, YW and Wong, F and Campochiaro, PA}, year={2005}, month={Jun}, pages={457–464} } @article{ghosh_wong_johansson_bruun_peters_2004, title={Transplantation of full-thickness retina in the rhodopsin transgenic pig}, volume={24}, ISSN={["0275-004X"]}, DOI={10.1097/00006982-200402000-00014}, abstractNote={Purpose To establish the morphology of full-thickness neuroretinal grafts transplanted to hosts with degenerative photoreceptor disease. Methods Twenty rhodopsin transgenic pigs received a neuroretinal sheet from a neonatal normal pig in one eye. Following vitrectomy and retinotomy with bleb formation, the grafts were positioned inside the bleb between the host neuroretina and retinal pigment epithelium. After a survival time of 4 months, eye specimens were studied by light and electron microscopy as well as with immunohistochemical markers. Results One eye developed endophthalmitis in the immediate postoperative period and was terminated. Laminated grafts with correct polarity were found in 13 of the remaining 19 eyes. In most cases, these grafts had well-developed organized photoreceptors with outer segments apposed to the host retinal pigment epithelium. The inner layers of the graft contained mostly Müller cells. Both eyes of the hosts had a reduction of photoreceptor cells in most of the retina, while inner layers remained relatively intact. Conclusions Full-thickness neuroretinal grafts can be transplanted to a large animal host with photoreceptor degeneration. The transplantation procedure is relatively atraumatic to both graft and host tissue, and the grafts survive well for at least 4 months. The graft and host retina does not seem to form extensive neuronal contacts, and future work must be directed at stimulating such activity without disrupting the retinal neuronal organization.}, number={1}, journal={RETINA-THE JOURNAL OF RETINAL AND VITREOUS DISEASES}, author={Ghosh, F and Wong, F and Johansson, K and Bruun, A and Peters, RM}, year={2004}, month={Feb}, pages={98–109} } @article{mahmoud_mccuen_hao_moon_tatebayashi_stinnett_petters_wong_2003, title={Lensectomy and vitrectomy decrease the rate of photoreceptor loss in rhodopsin P347L transgenic pigs}, volume={241}, ISSN={["0721-832X"]}, DOI={10.1007/s00417-003-0637-5}, abstractNote={{"Label"=>"BACKGROUND", "NlmCategory"=>"BACKGROUND"} Photoreceptor degeneration in retinitis pigmentosa (RP) runs an inevitable, gradually progressive course. A wide variety of growth factors of different origins have been shown to slow the rate of degeneration in some rodent models of RP. Recently, lens-derived neurotrophic factors have been shown to rescue degenerating ganglion cells in crush models of the optic nerve. Our objective was to evaluate the potential rescue effect of lensectomy and vitrectomy (L&V) on photoreceptor degeneration in a large-animal model, the rhodopsin P347L transgenic pig. {"Label"=>"METHODS", "NlmCategory"=>"METHODS"} We operated on one eye of each of 49 3-week-old pigs--15 vitrectomies and 34 L&V, 6 of which received steroids. Retinal paraffin sections were prepared for all eyes, in addition to immunohistochemistry in four eyes, 8 weeks after L&V. {"Label"=>"RESULTS", "NlmCategory"=>"RESULTS"} At eight weeks after L&V, operated eyes showed significantly more nuclei in the outer nuclear layer (ONL) than the unoperated fellow eyes. The better preservation of the ONL persisted but was less prominent by 20 weeks after surgery. Steroid treatment did not markedly reduce the better preservation of the ONL seen at 8, 10, and 12 weeks after surgery. The significant difference in cell count between operated and unoperated eyes in the L&V group at 8 weeks was due to the difference in the number of rods, not the cones. {"Label"=>"CONCLUSION", "NlmCategory"=>"CONCLUSIONS"} Lensectomy and vitrectomy delay photoreceptor degeneration in rhodopsin P347L transgenic pigs. Lens-related rescue effect is a probable reason for the delayed degeneration.}, number={4}, journal={GRAEFES ARCHIVE FOR CLINICAL AND EXPERIMENTAL OPHTHALMOLOGY}, author={Mahmoud, TH and McCuen, BW and Hao, Y and Moon, SJ and Tatebayashi, M and Stinnett, S and Petters, RA and Wong, F}, year={2003}, month={Apr}, pages={298–308} } @article{sommer_collins_neiding_rozeboom_wong_petters_2002, title={Conservation and regeneration of transgenic lines of swine by semen cryopreservation and artificial insemination}, volume={31}, number={1}, journal={Lab Animal}, author={Sommer, J. R. and Collins, E. B. and Neiding, T. and Rozeboom, K. and Wong, F. and Petters, R. M.}, year={2002}, pages={25–31} } @article{rodriguez_petters_crosier_farin_2002, title={Roles of gene transcription and PKA subtype activation in maturation of murine oocytes}, volume={123}, DOI={10.1530/rep.0.1230799}, abstractNote={The aims of this study were to examine the role of transcription and the coincident involvement of type I and type II protein kinase A (PKA) in the resumption of meiosis in murine cumulus-oocyte complexes (COCs) using the transcriptional inhibitors 5,6-dichloro-1-beta-D-ribofuranosylbenzimidazole (DRB) and alpha-amanitin. The first series of experiments was designed to: (i) characterize the role of transcription in gonadotrophin-mediated and spontaneous maturation of murine oocytes; (ii) examine the roles of specific gonadotrophins (FSH versus hCG) and cumulus cells in transcriptionally mediated oocyte maturation; and (iii) determine the reversibility of the transcriptional arrest of meiosis. In the presence of FSH, transcriptional inhibitors arrested germinal vesicle breakdown (GVBD) (DRB: 2 +/- 2% and control: 76 +/- 2%; alpha-amanitin: 4 +/- 4% and control: 70 +/- 4%). Furthermore, cumulus cells were required for transcriptional inhibitors to arrest GVBD (DRB with cumulus cells: 0 +/- 15%; DRB without cumulus cells: 94 +/- 13%; alpha-amanitin with cumulus cells: 15 +/- 2%; alpha-amanitin without cumulus cells: 99 +/- 2%). Thus, in mice, FSH-mediated GVBD uses a transcriptional mechanism, which probably occurs within the cumulus cell compartment. In a second series of experiments, the role of transcription in mediating the resumption of meiosis after activation of either type I or type II PKA was examined. Activation of type I PKA in murine COCs resulted in an arrest of GVBD that was independent of a transcriptional event (with DRB: 7 +/- 9% GVBD; without DRB: 11 +/- 9% GVBD). In contrast, activation of type II PKA resulted in a resumption of meiosis, which required the occurrence of gene transcription (with DRB: 12 +/- 9% GVBD; without DRB: 80 +/- 9% GVBD). As FSH binding to cumulus cells activates the PKA second messenger system, our results indicate that, in cultured murine COCs, FSH binding to cumulus cells results in the activation of type II PKA, which, in turn, mediates a downstream transcriptional event required for the initiation of GVBD.}, number={6}, journal={Reproduction (Cambridge, England)}, author={Rodriguez, K. F. and Petters, R. M. and Crosier, A. E. and Farin, C. E.}, year={2002}, pages={799–806} } @article{shaw_skold_wong_petters_hauswirth_lewin_2001, title={An allele-specific hammerhead ribozyme gene therapy for a porcine model of autosomal dominant retinitis pigmentosa}, volume={7}, number={2}, journal={Molecular Vision}, author={Shaw, L. C. and Skold, A. and Wong, F. and Petters, R. and Hauswirth, W. and Lewin, A. S.}, year={2001}, pages={6–13} } @article{blackmon_peng_hao_moon_oliveira_tatebayashi_petters_wong_2000, title={Early loss of synaptic protein PSD-95 from rod terminals of rhodopsin P347L transgenic porcine retina}, volume={885}, ISSN={["0006-8993"]}, DOI={10.1016/S0006-8993(00)02928-0}, abstractNote={Retinitis pigmentosa (RP), a type of retinal degeneration involving first rod and then slow cone photoreceptor degeneration, can be caused by any of a number of mutations in different genes. In the cases of mutations affecting rod-specific genes such as rhodopsin, it is unclear how the mutations may cause degeneration of cones. We have used the porcine retina, which is rod-dominated and has an abundance of cones, to study the mutation-induced changes in both rod and cone photoreceptors. Like patients with the same mutation, rhodopsin P347L transgenic swine manifest rod–cone degeneration. In addition, the rod bipolar cells fail to form synaptic connections with rods; instead, they form ectopic synapses with cones. The mechanisms that prevent the formation of the rod–rod bipolar cell synaptic connection are not known. We used specific antibodies and immunocytochemistry to show that the synaptic protein, PSD-95, is present in both normal and transgenic porcine retinas. During neonatal development, however, PSD-95 is lost from rod terminals in the transgenic swine. This loss is virtually complete (90%) by postnatal day 5, at a time when greater than 80% of rod cell bodies still remain. Furthermore, the remaining rods retain their outer segments and their gross morphology appears relatively normal. In contrast, PSD-95 expression continues in cone terminals, even in 10-month-old transgenic swine, where the rods have all disappeared and the cones show signs of severe degeneration. These results suggest that loss of PSD-95 may not be a general consequence of the deteriorating cell. Rather, the very early and selective loss of PSD-95 from the rod terminals may be causally related to the absence of rod–rod bipolar cell synapses in the rhodopsin P347L transgenic retina.}, number={1}, journal={BRAIN RESEARCH}, author={Blackmon, SM and Peng, YW and Hao, Y and Moon, SJ and Oliveira, LB and Tatebayashi, M and Petters, RM and Wong, F}, year={2000}, month={Dec}, pages={53–61} } @article{peng_hao_petters_wong_2000, title={Ectopic synaptogenesis in the mammalian retina caused by rod photoreceptor-specific mutations}, volume={3}, ISSN={["1097-6256"]}, DOI={10.1038/80639}, abstractNote={In addition to rod photoreceptor loss, many mutations in rod photoreceptor-specific genes cause degeneration of other neuronal types. Identifying mechanisms of cell-cell interactions initiated by rod-specific mutations and affecting other retinal cells is important for understanding the pathogenesis and progression of retinal degeneration. Here we show in animals with rod and cone degeneration due to mutations in the genes encoding rhodopsin and cGMP phosphodiesterase beta-subunit (PDE-beta) respectively, that rod bipolar cells received ectopic synapses from cones in the absence of rods. Thus, synaptic plasticity links certain rod-specific mutations to retina-wide structural alterations that involve different types of neurons.}, number={11}, journal={NATURE NEUROSCIENCE}, author={Peng, YW and Hao, Y and Petters, RM and Wong, F}, year={2000}, month={Nov}, pages={1121–1127} } @misc{huang_cideciyan_aleman_banin_huang_syed_petters_wong_milam_jacobson_2000, title={Optical coherence tomography (OCT) abnormalities in rhodopsin mutant transgenic swine with retinal degeneration}, volume={70}, ISSN={["0014-4835"]}, DOI={10.1006/exer.1999.0793}, abstractNote={Realizar una revisión bibliográfica para describir la nomenclatura actual en la interpretación de las imágenes retinales de la tomografía de coherencia óptica (OCT) en el área macular.Búsqueda exhaustiva de la bibliografía en las principales bases de datos biomédicas desde la introducción de la OCT en el campo oftalmológico.Las variantes cuantitativas del espesor macular central y la terminología utilizada a lo largo de los años está en relación directa con la tecnología y el equipamiento utilizado.La nomenclatura actual de la arquitectura macular normal representada en imágenes en vivo por la tecnología de OCT de dominio espectral nos proporciona una clara y válida interpretación anatómica para aplicarla no solo en proyectos de investigación, sino en la práctica diaria.To review the literature in order to describe the current nomenclature for the interpretation of retinal images of optical coherence tomography (OCT) in the macular area.A comprehensive literature search was conducted in the major biomedical databases since the introduction of OCT in ophthalmological field.Quantitative variations of central macular thickness and proper terminology used throughout the years are directly related to the technology and equipment used.The current nomenclature of normal macular architecture represented in vivo on spectral domain OCT technology provides a clear and valid anatomical interpretation that can be applied, not only in research, but also in everyday practice.}, number={2}, journal={EXPERIMENTAL EYE RESEARCH}, author={Huang, YJ and Cideciyan, AV and Aleman, TS and Banin, E and Huang, JC and Syed, NA and Petters, RM and Wong, F and Milam, AH and Jacobson, SG}, year={2000}, month={Feb}, pages={247–251} } @article{petters_sommer_2000, title={Transgenic animals as models for human disease}, volume={9}, ISSN={["0962-8819"]}, DOI={10.1023/A:1008926303533}, abstractNote={Transgenic animals, especially mice, have been used quite extensively as models for various human diseases. At first, the level of scientific inquiry was driven by the need to establish the model. In many cases, these models may be considered quite crude because of their limitations. More recently, transgenic models of disease have become more refined and are currently being used to study the pathological mechanisms behind the disease rather than to just provide a model of the disease. Using some examples from the recent literature, we will document the current level and complexity of inquiry using transgenic animals. New techniques and techniques that may prove promising will be discussed.}, number={4-5}, journal={TRANSGENIC RESEARCH}, author={Petters, RM and Sommer, JR}, year={2000}, month={Jan}, pages={347–351} } @article{rodriguez_petters_farin_1999, title={Gonadotropin-induced germinal vesicle breakdown in the mouse requires gene transcription.}, volume={60}, number={1999}, journal={Biology of Reproduction}, author={Rodriguez, K. F. and Petters, R. M. and Farin, C. E.}, year={1999}, pages={214} } @article{banin_cideciyan_aleman_petters_wong_milam_jacobson_1999, title={Retinal rod photoreceptor-specific gene mutation perturbs cone pathway development}, volume={23}, ISSN={["1097-4199"]}, DOI={10.1016/s0896-6273(00)80807-7}, abstractNote={Rod-specific photoreceptor dystrophies are complicated by the delayed death of genetically normal neighboring cones. In transgenic (Tg) swine with a rod-specific (rhodopsin) gene mutation, cone photoreceptor physiology was normal for months but later declined, consistent with delayed cone cell death. Surprisingly, cone postreceptoral function was markedly abnormal when cone photoreceptor physiology was still normal. The defect was localized to hyperpolarizing cells postsynaptic to the middle wavelength-sensitive cones. Recordings throughout postnatal development indicated a failure of cone circuitry maturation, a novel mechanism of secondary cone abnormality in rod dystrophy. The results have implications for therapy for human retinal dystrophies and raise the possibility that rod afferent activity plays a role in the postnatal maturation of cone retinal circuitry.}, number={3}, journal={NEURON}, author={Banin, E and Cideciyan, AV and Aleman, TS and Petters, RM and Wong, F and Milam, AH and Jacobson, SG}, year={1999}, month={Jul}, pages={549–557} } @article{illera_lorenzo_illera_petters_1998, title={Developmental competence of immature pig oocytes under the influence of EGF, IGF-I, follicular fluid and gonadotropins during IVM-IVF processes}, volume={42}, number={8}, journal={International Journal of Developmental Biology}, author={Illera, M. J. and Lorenzo, P. L. and Illera, J. C. and Petters, R. M.}, year={1998}, pages={1169–1172} } @article{li_wong_chang_possin_hao_petters_milam_1998, title={Rhodopsin transgenic pigs as a model for human retinitis pigmentosa}, volume={39}, number={5}, journal={Investigative Ophthalmology and Visual Science}, author={Li, Z. Y. and Wong, F. and Chang, J. H. and Possin, D. E. and Hao, Y. and Petters, R. M. and Milam, A. H}, year={1998}, pages={808–819} } @article{petters_alexander_wells_collins_sommer_blanton_rojas_hao_flowers_banin_et al._1997, title={Genetically engineered large animal model for studying cone photoreceptor survival and degeneration in retinitis pigmentosa}, volume={15}, ISSN={["1087-0156"]}, DOI={10.1038/nbt1097-965}, abstractNote={Patients with retinitis pigmentosa (RP) typically develop night blindness early in life due to loss of rod photoreceptors. The remaining cone photoreceptors are the mainstay of their vision; however, over years or decades, these cones slowly degenerate, leading to blindness. We created transgenic pigs that express a mutated rhodopsin gene (Pro347Leu). Like RP patients with the same mutation, these pigs have early and severe rod loss; initially their cones are relatively spared, but these surviving cones slowly degenerate. By age 20 months, there is only a single layer of morphologically abnormal cones and the cone electroretinogram is markedly reduced. Given the strong similarities in phenotype to that of RP patients, these transgenic pigs will provide a large animal model for study of the protracted phase of cone degeneration found in RP and for preclinical treatment trials.}, number={10}, journal={NATURE BIOTECHNOLOGY}, author={Petters, RM and Alexander, CA and Wells, KD and Collins, EB and Sommer, JR and Blanton, MR and Rojas, G and Hao, Y and Flowers, WL and Banin, E and et al.}, year={1997}, month={Oct}, pages={965–970} } @article{petters_1994, title={TRANSGENIC LIVESTOCK AS GENETIC MODELS OF HUMAN-DISEASE}, volume={6}, ISSN={["1448-5990"]}, DOI={10.1071/RD9940643}, abstractNote={Genetic models of human disease can lead to new insights concerning disease aetiology or suggest novel therapeutic interventions. Livestock species, especially pigs, cows, sheep and horses, are often good animal models of human disease. However, genetic models in livestock species have included only the study of spontaneous mutations. Production of transgenic livestock is now possible but owing to a low efficiency of production, it is very expensive and its application limited. Anticipated application of improved technologies such as embryonic stem cells and homologous recombination will allow for increased sophistication of experimental design and wider use of genetically modified livestock. In all cases, the appropriate species for a genetic model of human disease should be the species which best models the physiology of the organ or system under consideration. In the future, livestock will play an increasingly more important role in biomedical research through the application of genetic engineering methodologies.}, number={5}, journal={REPRODUCTION FERTILITY AND DEVELOPMENT}, author={PETTERS, RM}, year={1994}, pages={643–645} } @article{petters_1992, title={EMBRYO DEVELOPMENT INVITRO TO THE BLASTOCYST STAGE IN CATTLE, PIGS AND SHEEP}, volume={28}, ISSN={["0378-4320"]}, DOI={10.1016/0378-4320(92)90128-Z}, abstractNote={Schemes for the in vitro production of embryos as well as embryo manipulations such as nuclear transfer (cloning) and gene transfer require the ability to culture embryos from the zygote to the blastocyst stage in vitro while maintaining embryo viability. For cattle, pig or sheep embryos, significant problems have been encountered in achieving development to the blastocyst stage due to ‘in vitro development blocks’. These blocks can be overcome now, either with complex solutions such as co-culture with other cells or with simple solutions like minor modifications of the culture medium. Some data indicate significant differences between in vitro cultured and in vivo embryos which may account for differences in survival after embryo transfer. Even so, success of embryo culture is high enough to warrant considerable optimism about further improvements in the efficiency of many embryo technologies.}, number={1-4}, journal={ANIMAL REPRODUCTION SCIENCE}, author={PETTERS, RM}, year={1992}, month={Jul}, pages={415–421} } @article{petters_johnson_reed_archibong_1990, title={Glucose, glutamine and inorganic phosphate in early development of the pig embryo in vitro}, volume={89}, DOI={10.1530/jrf.0.0890269}, abstractNote={Pig embryos at the 1- or 2-cell stage (before the 'block' to development in vitro) were cultured in 8 different media derived from Krebs'-Ringer-bicarbonate medium. A 2 x 2 x 2 factorial arrangement was used for the treatments, with glucose, glutamine and phosphate being the major effects tested. Embryos were obtained from sows approximately 44-48 h after the observation of oestrus, with the majority being at the 1-cell stage. Embryos from each female were randomly assigned to each treatment. After in-vitro culture, all embryos were scored for the stage of development attained and stained to determine final cell number. Significant effects were evident due to female, glucose, glutamine, a phosphate x glucose interaction and a glutamine x glucose interaction. None of the media components tested was inhibitory to embryo development. The greatest development (45-60% morula or blastocyst) was achieved with glucose and glutamine (both alone and in combination) in the media, demonstrating that an amino acid can serve as the sole energy source for complete preimplantation embryonic development in vitro.}, number={1}, journal={Journal of Reproduction & Fertility}, author={Petters, R. M. and Johnson, B. H. and Reed, M. L. and Archibong, A. E.}, year={1990}, pages={269} } @article{petters_1986, title={Recombinant DNA, gene transfer and the future of animal agriculture}, volume={62}, number={6}, journal={Journal of Animal Science}, author={Petters, R. M.}, year={1986}, pages={1759} } @article{petters_grosch_olson_1978, title={FLIGHTLESS MUTATION IN WASP HABROBRACON-JUGLANDIS}, volume={69}, ISSN={["0022-1503"]}, DOI={10.1093/oxfordjournals.jhered.a108891}, number={2}, journal={JOURNAL OF HEREDITY}, author={PETTERS, RM and GROSCH, DS and OLSON, CS}, year={1978}, pages={113–116} } @article{petters_grosch_1977, title={REPRODUCTIVE-PERFORMANCE OF BRACON-HEBETOR (HYMENOPTERA-BRACONIDAE) FEMALES WITH MORE OR FEWER THAN NORMAL NUMBER OF OVARIOLES}, volume={70}, ISSN={["0013-8746"]}, DOI={10.1093/aesa/70.4.577}, abstractNote={After recording the daily egg production of Bracon hebetor Say females (Whiting stock No. 33) for 5 days, we dissected them to determine their number of ovarioles. Wasps with fewer than 4 ovarioles (1, 2, or 3) produced proportionately fewer eggs than their “normal” 4-ovariole sisters. In females with 5–9 ovarioles, egg production did not increase significantly. The supply of vitellogenic materials is a limiting factor. Individuals with a decrease in ovarioles were obtained by screening large samples of untreated stocks. Supernumerary ovarioles were induced by cold storage of fourth instars.}, number={4}, journal={ANNALS OF THE ENTOMOLOGICAL SOCIETY OF AMERICA}, author={PETTERS, RM and GROSCH, DS}, year={1977}, pages={577–582} }