@article{lee_kwon_aylor_marchuk_2022, title={A cross-species approach using an in vivo evaluation platform in mice demonstrates that sequence variation in human RABEP2 modulates ischemic stroke outcomes}, volume={109}, ISSN={["1537-6605"]}, DOI={10.1016/j.ajhg.2022.09.003}, abstractNote={Ischemic stroke, caused by vessel blockage, results in cerebral infarction, the death of brain tissue. Previously, quantitative trait locus (QTL) mapping of cerebral infarct volume and collateral vessel number identified a single, strong genetic locus regulating both phenotypes. Additional studies identified RAB GTPase-binding effector protein 2 (Rabep2) as the casual gene. However, there is yet no evidence that variation in the human ortholog of this gene plays any role in ischemic stroke outcomes. We established an in vivo evaluation platform in mice by using adeno-associated virus (AAV) gene replacement and verified that both mouse and human RABEP2 rescue the mouse Rabep2 knockout ischemic stroke volume and collateral vessel phenotypes. Importantly, this cross-species complementation enabled us to experimentally investigate the functional effects of coding sequence variation in human RABEP2. We chose four coding variants from the human population that are predicted by multiple in silico algorithms to be damaging to RABEP2 function. In vitro and in vivo analyses verify that all four led to decreased collateral vessel connections and increased infarct volume. Thus, there are naturally occurring loss-of-function alleles. This cross-species approach will expand the number of targets for therapeutics development for ischemic stroke.}, number={10}, journal={AMERICAN JOURNAL OF HUMAN GENETICS}, author={Lee, Han Kyu and Kwon, Do Hoon and Aylor, David L. and Marchuk, Douglas A.}, year={2022}, month={Oct}, pages={1814–1827} }
 @article{witchey_doyle_fredenburg_st armour_horman_odenkirk_aylor_baker_patisaul_2022, title={Impacts of Gestational FireMaster 550 (FM 550) Exposure on the Neonatal Cortex are Sex Specific and Largely Attributable to the Organophosphate Esters}, volume={9}, ISSN={["1423-0194"]}, DOI={10.1159/000526959}, abstractNote={<b><i>Introduction:</i></b> Flame retardants (FRs) are common bodily and environmental pollutants, creating concern about their potential toxicity. We and others have found that the commercial mixture FireMaster® 550 (FM 550) or its individual brominated (BFR) and organophosphate ester (OPFR) components are potential developmental neurotoxicants. Using Wistar rats, we previously reported that developmental exposure to FM 550 or its component classes produced sex- and compound-specific effects on adult socioemotional behaviors. The underlying mechanisms driving the behavioral phenotypes are unknown. <b><i>Methods:</i></b> To further mechanistic understanding, here we conducted transcriptomics in parallel with a novel lipidomics approach using cortical tissues from newborn siblings of the rats in the published behavioral study. Inclusion of lipid composition is significant because it is rarely examined in developmental neurotoxicity studies. Pups were gestationally exposed via oral dosing to the dam to FM 550 or the BFR or OPFR components at environmentally relevant doses. <b><i>Results:</i></b> The neonatal cortex was highly sexually dimorphic in lipid and transcriptome composition, and males were more significantly impacted by FR exposure. Multiple adverse modes of action for the BFRs and OPFRs on neurodevelopment were identified, with the OPFRs being more disruptive than the BFRs via multiple mechanisms including dysregulation of mitochondrial function and disruption of cholinergic and glutamatergic systems. Disrupted mitochondrial function by environmental factors has been linked to a higher risk of autism spectrum disorders and neurodegenerative disorders. Impacted lipid classes included ceramides, sphingomyelins, and triacylglycerides. Robust ceramide upregulation in the OPFR females could suggest a heightened risk of brain metabolic disease. <b><i>Conclusions:</i></b> This study reveals multiple mechanisms by which the components of a common FR mixture are developmentally neurotoxic and that the OPFRs may be the compounds of greatest concern. }, journal={NEUROENDOCRINOLOGY}, author={Witchey, S. K. and Doyle, M. G. and Fredenburg, J. D. and St Armour, G. and Horman, B. and Odenkirk, M. T. and Aylor, D. L. and Baker, E. S. and Patisaul, H. B.}, year={2022}, month={Sep} }
 @article{lee_wetzel-strong_aylor_marchuk_2021, title={A Neuroprotective Locus Modulates Ischemic Stroke Infarction Independent of Collateral Vessel Anatomy}, volume={15}, ISSN={["1662-453X"]}, DOI={10.3389/fnins.2021.705160}, abstractNote={Although studies with inbred strains of mice have shown that infarct size is largely determined by the extent of collateral vessel connections between arteries in the brain that enable reperfusion of the ischemic territory, we have identified strain pairs that do not vary in this vascular phenotype, but which nonetheless exhibit large differences in infarct size. In this study we performed quantitative trait locus (QTL) mapping in mice from an intercross between two such strains, WSB/EiJ (WSB) and C57BL/6J (B6). This QTL mapping revealed only one neuroprotective locus on Chromosome 8 (Chr 8) that co-localizes with a neuroprotective locus we mapped previously from F2 progeny between C3H/HeJ (C3H) and B6. The allele-specific phenotypic effect on infarct volume at the genetic region identified by these two independent mappings was in the opposite direction of the parental strain phenotype; namely, the B6 allele conferred increased susceptibility to ischemic infarction. Through two reciprocal congenic mouse lines with either the C3H or B6 background at the Chr 8 locus, we verified the neuroprotective effects of this genetic region that modulates infarct volume without any effect on the collateral vasculature. Additionally, we surveyed non-synonymous coding SNPs and performed RNA-sequencing analysis to identify potential candidate genes within the genetic interval. Through these approaches, we suggest new genes for future mechanistic studies of infarction following ischemic stroke, which may represent novel gene/protein targets for therapeutic development.}, journal={FRONTIERS IN NEUROSCIENCE}, author={Lee, Han Kyu and Wetzel-Strong, Sarah E. and Aylor, David L. and Marchuk, Douglas A.}, year={2021}, month={Aug} }
 @article{widmayer_handel_aylor_2020, title={Age and Genetic Background Modify Hybrid Male Sterility in House Mice}, volume={216}, ISSN={["1943-2631"]}, DOI={10.1534/genetics.120.303474}, abstractNote={Abstract}, number={2}, journal={GENETICS}, author={Widmayer, Samuel J. and Handel, Mary Ann and Aylor, David L.}, year={2020}, month={Oct}, pages={585–597} }
 @article{garbutt_konganti_konneker_hillhouse_phelps_jones_aylor_threadgill_2020, title={Derivation of stable embryonic stem cell-like, but transcriptionally heterogenous, induced pluripotent stem cells from non-permissive mouse strains}, volume={31}, ISSN={["1432-1777"]}, DOI={10.1007/s00335-020-09849-x}, abstractNote={Genetic background is known to play a role in the ability to derive pluripotent, embryonic stem cells (ESC), a trait referred to as permissiveness. Previously we demonstrated that induced pluripotent stem cells (iPSC) can be readily derived from non-permissive mouse strains by addition of serum-based media supplemented with GSK3B and MEK inhibitors, termed 2iS media, 3 days into reprogramming. Here, we describe the derivation of second type of iPSC colony from non-permissive mouse strains that can be stably maintained independently of 2iS media. The resulting cells display transcriptional heterogeneity similar to that observed in ESC from permissive genetic backgrounds derived in conventional serum containing media supplemented with leukemia inhibitor factor. However, unlike previous studies that report exclusive subpopulations, we observe both exclusive and simultaneous expression of naive and primed cell surface markers. Herein, we explore shifts in pluripotency in the presence of 2iS and characterize heterogenous subpopulations to determine their pluripotent state and role in heterogenous iPSCs derived from the non-permissive NOD/ShiLtJ strain. We conclude that heterogeneity is a naturally occurring, necessary quality of stem cells that allows for the maintenance of pluripotency. This study further demonstrates the efficacy of the 2iS reprogramming technique. It is also the first study to derive stable ESC-like stem cells from the non-permissive NOD/ShiLtJ and WSB/EiJ strains, enabling easier and broader research possibilities into pluripotency for these and similar non-permissive mouse strains and species.}, number={9-12}, journal={MAMMALIAN GENOME}, publisher={Springer Science and Business Media LLC}, author={Garbutt, Tiffany A. and Konganti, Kranti and Konneker, Thomas and Hillhouse, Andrew and Phelps, Drake and Jones, Alexis and Aylor, David and Threadgill, David W.}, year={2020}, month={Dec}, pages={263–286} }
 @article{lee_widmayer_huang_aylor_marchuk_2019, title={Novel Neuroprotective Loci Modulating Ischemic Stroke Volume in Wild-Derived Inbred Mouse Strains}, volume={213}, ISSN={["1943-2631"]}, DOI={10.1534/genetics.119.302555}, abstractNote={Abstract}, number={3}, journal={GENETICS}, author={Lee, Han Kyu and Widmayer, Samuel J. and Huang, Min-Nung and Aylor, David L. and Marchuk, Douglas A.}, year={2019}, month={Nov}, pages={1079–1092} }
 @article{patisaul_fenton_aylor_2018, title={Animal models of endocrine disruption}, volume={32}, ISSN={["1532-1908"]}, DOI={10.1016/j.beem.2018.03.011}, abstractNote={Endocrine disrupting chemicals (EDCs) are compounds that alter the structure and function of the endocrine system and may be contributing to disorders of the reproductive, metabolic, neuroendocrine and other complex systems. Typically, these outcomes cannot be modeled in cell-based or other simple systems necessitating the use of animal testing. Appropriate animal model selection is required to effectively recapitulate the human experience, including relevant dosing and windows of exposure, and ensure translational utility and reproducibility. While classical toxicology heavily relies on inbred rats and mice, and focuses on apical endpoints such as tumor formation or birth defects, EDC researchers have used a greater diversity of species to effectively model more subtle but significant outcomes such as changes in pubertal timing, mammary gland development, and social behaviors. Advances in genomics, neuroimaging and other tools are making a wider range of animal models more widely available to EDC researchers.}, number={3}, journal={BEST PRACTICE & RESEARCH CLINICAL ENDOCRINOLOGY & METABOLISM}, author={Patisaul, Heather B. and Fenton, Suzanne E. and Aylor, David}, year={2018}, month={Jun}, pages={283–297} }
 @article{garbutt_konneker_konganti_hillhouse_swift-haire_jones_phelps_aylor_threadgill_2018, title={Permissiveness to form pluripotent stem cells may be an evolutionarily derived characteristic in Mus muscuius}, volume={8}, ISSN={["2045-2322"]}, url={https://doi.org/10.1038/s41598-018-32116-8}, DOI={10.1038/s41598-018-32116-8}, abstractNote={Abstract}, journal={SCIENTIFIC REPORTS}, author={Garbutt, Tiffany A. and Konneker, Thomas I and Konganti, Kranti and Hillhouse, Andrew E. and Swift-Haire, Francis and Jones, Alexis and Phelps, Drake and Aylor, David L. and Threadgill, David W.}, year={2018}, month={Oct} }
 @article{venkatratnam_house_konganti_mckenney_threadgill_chiu_aylor_wright_rusyn_2018, title={Population-based dose-response analysis of liver transcriptional response to trichloroethylene in mouse}, volume={29}, ISSN={["1432-1777"]}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-85040693289&partnerID=MN8TOARS}, DOI={10.1007/s00335-018-9734-y}, abstractNote={Studies of gene expression are common in toxicology and provide important clues to mechanistic understanding of adverse effects of chemicals. Most prior studies have been performed in a single strain or cell line; however, gene expression is heavily influenced by the genetic background, and these genotype-expression differences may be key drivers of inter-individual variation in response to chemical toxicity. In this study, we hypothesized that the genetically diverse Collaborative Cross mouse population can be used to gain insight and suggest mechanistic hypotheses for the dose- and genetic background-dependent effects of chemical exposure. This hypothesis was tested using a model liver toxicant trichloroethylene (TCE). Liver transcriptional responses to TCE exposure were evaluated 24 h after dosing. Transcriptomic dose–responses were examined for both TCE and its major oxidative metabolite trichloroacetic acid (TCA). As expected, peroxisome- and fatty acid metabolism-related pathways were among the most dose–responsive enriched pathways in all strains. However, nearly half of the TCE-induced liver transcriptional perturbation was strain-dependent, with abundant evidence of strain/dose interaction, including in the peroxisomal signaling-associated pathways. These effects were highly concordant between the administered TCE dose and liver levels of TCA. Dose–response analysis of gene expression at the pathway level yielded points of departure similar to those derived from the traditional toxicology studies for both non-cancer and cancer effects. Mapping of expression–genotype–dose relationships revealed some significant associations; however, the effects of TCE on gene expression in liver appear to be highly polygenic traits that are challenging to positionally map. This study highlights the usefulness of mouse population-based studies in assessing inter-individual variation in toxicological responses, but cautions that genetic mapping may be challenging because of the complexity in gene exposure–dose relationships.}, number={1-2}, journal={MAMMALIAN GENOME}, author={Venkatratnam, Abhishek and House, John S. and Konganti, Kranti and McKenney, Connor and Threadgill, David W. and Chiu, Weihsueh A. and Aylor, David L. and Wright, Fred A. and Rusyn, Ivan}, year={2018}, month={Feb}, pages={168–181} }
 @article{wang_pehrsson_purushotham_li_zhuo_zhang_lawson_province_krapp_lan_et al._2018, title={The NIEHS TaRGET II Consortium and environmental epigenomics}, volume={36}, ISSN={1087-0156 1546-1696}, url={http://dx.doi.org/10.1038/NBT.4099}, DOI={10.1038/NBT.4099}, number={3}, journal={Nature Biotechnology}, publisher={Springer Science and Business Media LLC}, author={Wang, Ting and Pehrsson, Erica C and Purushotham, Deepak and Li, Daofeng and Zhuo, Xiaoyu and Zhang, Bo and Lawson, Heather A and Province, Michael A and Krapp, Christopher and Lan, Yemin and et al.}, year={2018}, month={Mar}, pages={225–227} }
 @misc{wang_pehrsson_purushotham_li_zhuo_zhang_lawson_province_krapp_lan_et al._2018, title={The NIEHS TaRGET II Consortium and environmental epigenomics}, volume={36}, number={3}, journal={Nature Biotechnology}, author={Wang, T. and Pehrsson, E. C. and Purushotham, D. and Li, D. F. and Zhuo, X. Y. and Zhang, B. and Lawson, H. A. and Province, M. A. and Krapp, C. and Lan, Y. M. and et al.}, year={2018}, pages={225–227} }
 @article{venkatratnam_furuya_kosyk_gold_bodnar_konganti_threadgill_gillespie_aylor_wright_et al._2017, title={Editor's Highlight: Collaborative Cross Mouse Population Enables Refinements to Characterization of the Variability in Toxicokinetics of Trichloroethylene and Provides Genetic Evidence for the Role of PPAR Pathway in Its Oxidative Metabolism}, volume={158}, ISSN={["1096-0929"]}, DOI={10.1093/toxsci/kfx065}, abstractNote={Background
Trichloroethylene (TCE) is a known carcinogen in humans and rodents. Previous studies of inter-strain variability in TCE metabolism were conducted in multi-strain panels of classical inbred mice with limited genetic diversity to identify gene-environment interactions associated with chemical exposure.


Objectives
To evaluate inter-strain variability in TCE metabolism and identify genetic determinants that are associated with TCE metabolism and effects using Collaborative Cross (CC), a large panel of genetically diverse strains of mice.


Methods
We administered a single oral dose of 0, 24, 80, 240, or 800 mg/kg of TCE to mice from 50 CC strains, and collected organs 24 h post-dosing. Levels of trichloroacetic acid (TCA), a major oxidative metabolite of TCE were measured in multiple tissues. Protein expression and activity levels of TCE-metabolizing enzymes were evaluated in the liver. Liver transcript levels of known genes perturbed by TCE exposure were also quantified. Genetic association mapping was performed on the acquired phenotypes.


Results
TCA levels varied in a dose- and strain-dependent manner in liver, kidney, and serum. The variability in TCA levels among strains did not correlate with expression or activity of a number of enzymes known to be involved in TCE oxidation. Peroxisome proliferator-activated receptor alpha (PPARα)-responsive genes were found to be associated with strain-specific differences in TCE metabolism.


Conclusions
This study shows that CC mouse population is a valuable tool to quantitatively evaluate inter-individual variability in chemical metabolism and to identify genes and pathways that may underpin population differences.}, number={1}, journal={TOXICOLOGICAL SCIENCES}, author={Venkatratnam, Abhishek and Furuya, Shinji and Kosyk, Oksana and Gold, Avram and Bodnar, Wanda and Konganti, Kranti and Threadgill, David W. and Gillespie, Kevin M. and Aylor, David L. and Wright, Fred A. and et al.}, year={2017}, month={Jul}, pages={48–62} }
 @article{shorter_odet_aylor_pan_kao_fu_morgan_greenstein_bell_stevans_et al._2017, title={Male Infertility Is Responsible for Nearly Half of the Extinction Observed in the Mouse Collaborative Cross}, volume={206}, ISSN={["1943-2631"]}, DOI={10.1534/genetics.116.199596}, abstractNote={Abstract}, number={2}, journal={GENETICS}, author={Shorter, John R. and Odet, Fanny and Aylor, David L. and Pan, Wenqi and Kao, Chia-Yu and Fu, Chen-Ping and Morgan, Andrew P. and Greenstein, Seth and Bell, Timothy A. and Stevans, Alicia M. and et al.}, year={2017}, month={Jun}, pages={557–572} }
 @article{hunter_robinson_aylor_singh_2016, title={Genetic Background, Maternal Age, and Interaction Effects Mediate Rates of Crossing Over in Drosophila melanogaster Females}, volume={6}, ISSN={["2160-1836"]}, DOI={10.1534/g3.116.027631}, abstractNote={Abstract}, number={5}, journal={G3-GENES GENOMES GENETICS}, author={Hunter, Chad M. and Robinson, Matthew C. and Aylor, David L. and Singh, Nadia D.}, year={2016}, month={May}, pages={1409–1416} }
 @article{didion_morgan_clayshulte_mcmullan_yadgary_petkov_bell_gatti_crowley_hua_et al._2015, title={A Multi-Megabase Copy Number Gain Causes Maternal Transmission Ratio Distortion on Mouse Chromosome 2}, volume={11}, ISSN={["1553-7404"]}, DOI={10.1371/journal.pgen.1004850}, abstractNote={Significant departures from expected Mendelian inheritance ratios (transmission ratio distortion, TRD) are frequently observed in both experimental crosses and natural populations. TRD on mouse Chromosome (Chr) 2 has been reported in multiple experimental crosses, including the Collaborative Cross (CC). Among the eight CC founder inbred strains, we found that Chr 2 TRD was exclusive to females that were heterozygous for the WSB/EiJ allele within a 9.3 Mb region (Chr 2 76.9 – 86.2 Mb). A copy number gain of a 127 kb-long DNA segment (designated as responder to drive, R2d) emerged as the strongest candidate for the causative allele. We mapped R2d sequences to two loci within the candidate interval. R2d1 is located near the proximal boundary, and contains a single copy of R2d in all strains tested. R2d2 maps to a 900 kb interval, and the number of R2d copies varies from zero in classical strains (including the mouse reference genome) to more than 30 in wild-derived strains. Using real-time PCR assays for the copy number, we identified a mutation (R2d2WSBdel1) that eliminates the majority of the R2d2WSB copies without apparent alterations of the surrounding WSB/EiJ haplotype. In a three-generation pedigree segregating for R2d2WSBdel1, the mutation is transmitted to the progeny and Mendelian segregation is restored in females heterozygous for R2d2WSBdel1, thus providing direct evidence that the copy number gain is causal for maternal TRD. We found that transmission ratios in R2d2WSB heterozygous females vary between Mendelian segregation and complete distortion depending on the genetic background, and that TRD is under genetic control of unlinked distorter loci. Although the R2d2WSB transmission ratio was inversely correlated with average litter size, several independent lines of evidence support the contention that female meiotic drive is the cause of the distortion. We discuss the implications and potential applications of this novel meiotic drive system.}, number={2}, journal={PLOS GENETICS}, author={Didion, John P. and Morgan, Andrew P. and Clayshulte, Amelia M. -F. and Mcmullan, Rachel C. and Yadgary, Liran and Petkov, Petko M. and Bell, Timothy A. and Gatti, Daniel M. and Crowley, James J. and Hua, Kunjie and et al.}, year={2015}, month={Feb} }
 @article{crowley_zhabotynsky_sun_huang_pakatci_kim_wang_morgan_calaway_aylor_et al._2015, title={Analyses of allele-specific gene expression in highly divergent mouse crosses identifies pervasive allelic imbalance}, volume={47}, ISSN={1061-4036 1546-1718}, url={http://dx.doi.org/10.1038/NG.3222}, DOI={10.1038/NG.3222}, abstractNote={Fernando Pardo-Manuel de Villena and colleagues generate a 3 × 3 diallel cross of three inbred mouse lines and examine gene expression in multiple tissues. They identify allelic imbalance favoring the expression of the paternal allele across the genome. Complex human traits are influenced by variation in regulatory DNA through mechanisms that are not fully understood. Because regulatory elements are conserved between humans and mice, a thorough annotation of cis regulatory variants in mice could aid in further characterizing these mechanisms. Here we provide a detailed portrait of mouse gene expression across multiple tissues in a three-way diallel. Greater than 80% of mouse genes have cis regulatory variation. Effects from these variants influence complex traits and usually extend to the human ortholog. Further, we estimate that at least one in every thousand SNPs creates a cis regulatory effect. We also observe two types of parent-of-origin effects, including classical imprinting and a new global allelic imbalance in expression favoring the paternal allele. We conclude that, as with humans, pervasive regulatory variation influences complex genetic traits in mice and provide a new resource toward understanding the genetic control of transcription in mammals.}, number={4}, journal={Nature Genetics}, publisher={Springer Science and Business Media LLC}, author={Crowley, James J and Zhabotynsky, Vasyl and Sun, Wei and Huang, Shunping and Pakatci, Isa Kemal and Kim, Yunjung and Wang, Jeremy R and Morgan, Andrew P and Calaway, John D and Aylor, David L and et al.}, year={2015}, month={Mar}, pages={353–360} }
 @article{crowley_zhabotynsky_sun_huang_pakatci_kim_wang_morgan_calaway_aylor_et al._2015, title={Erratum: Corrigendum: Analyses of allele-specific gene expression in highly divergent mouse crosses identifies pervasive allelic imbalance}, volume={47}, ISSN={1061-4036 1546-1718}, url={http://dx.doi.org/10.1038/NG0615-690A}, DOI={10.1038/NG0615-690A}, abstractNote={Nat. Genet. 47, 353–360 (2015); published online 2 March 2015; corrected after print 16 April 2015 In the version of this article initially published, an accession number was not provided for RNA-seq data sets. The RNA-seq data sets that passed quality control are available at the Sequence Read Archive (SRA) under accession SRP056236.}, number={6}, journal={Nature Genetics}, publisher={Springer Nature}, author={Crowley, James J and Zhabotynsky, Vasyl and Sun, Wei and Huang, Shunping and Pakatci, Isa Kemal and Kim, Yunjung and Wang, Jeremy R and Morgan, Andrew P and Calaway, John D and Aylor, David L and et al.}, year={2015}, month={May}, pages={690–690} }
 @article{rebuli_camacho_adonay_reif_aylor_patisaul_2015, title={Impact of Low-Dose Oral Exposure to Bisphenol A (BPA) on Juvenile and Adult Rat Exploratory and Anxiety Behavior: A CLARITY-BPA Consortium Study}, volume={148}, ISSN={["1096-0929"]}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-84952932385&partnerID=MN8TOARS}, DOI={10.1093/toxsci/kfv163}, abstractNote={Bisphenol A (BPA) is a high volume production chemical and has been identified as an endocrine disruptor, prompting concern that developmental exposure could impact brain development and behavior. Rodent and human studies suggest that early life BPA exposure may result in an anxious, hyperactive phenotype but results are conflicting and data from studies using multiple doses below the no-observed-adverse-effect level are limited. To address this, the present studies were conducted as part of the CLARITY-BPA (Consortium Linking Academic and Regulatory Insights on BPA Toxicity) program. The impact of perinatal BPA exposure (2.5, 25, or 2500 µg/kg body weight (bw)/day) on behaviors related to anxiety and exploratory activity was assessed in juvenile (prepubertal) and adult NCTR Sprague-Dawley rats of both sexes. Ethinyl estradiol (0.5 µg/kg bw/day) was used as a reference estrogen. Exposure spanned gestation and lactation with dams gavaged from gestational day 6 until birth and then the offspring gavaged directly through weaning (n = 12/sex/group). Behavioral assessments included open field, elevated plus maze, and zero maze. Anticipated sex differences in behavior were statistically identified or suggested in most cases. No consistent effects of BPA were observed for any endpoint, in either sex, at either age compared to vehicle controls; however, significant differences between BPA-exposed and ethinyl estradiol-exposed groups were identified for some endpoints. Limitations of this study are discussed and include suboptimal statistical power and low concordance across behavioral tasks. These data do not indicate BPA-related effects on anxiety or exploratory activity in these developmentally exposed rats.}, number={2}, journal={TOXICOLOGICAL SCIENCES}, author={Rebuli, Meghan E. and Camacho, Luisa and Adonay, Maria E. and Reif, David M. and Aylor, David L. and Patisaul, Heather B.}, year={2015}, month={Dec}, pages={341–354} }
 @article{odet_pan_bell_goodson_stevans_yun_aylor_kao_mcmillan_villena_et al._2015, title={The Founder Strains of the Collaborative Cross Express a Complex Combination of Advantageous and Deleterious Traits for Male Reproduction}, volume={5}, ISSN={["2160-1836"]}, DOI={10.1534/g3.115.020172}, abstractNote={Abstract}, number={12}, journal={G3-GENES GENOMES GENETICS}, author={Odet, Fanny and Pan, Wenqi and Bell, Timothy A. and Goodson, Summer G. and Stevans, Alicia M. and Yun, Zianing and Aylor, David L. and Kao, Chia-Yu and McMillan, Leonard and Villena, Fernando Pardo-Manuel and et al.}, year={2015}, month={Dec}, pages={2671–2683} }
 @article{rutledge_aylor_carpenter_peck_chines_ostrowski_chesler_churchill_villena_kelada_2014, title={Genetic Regulation of Zfp30, CXCL1, and Neutrophilic Inflammation in Murine Lung}, volume={198}, ISSN={["1943-2631"]}, DOI={10.1534/genetics.114.168138}, abstractNote={Abstract}, number={2}, journal={GENETICS}, author={Rutledge, Holly and Aylor, David L. and Carpenter, Danielle E. and Peck, Bailey C. and Chines, Peter and Ostrowski, Lawrence E. and Chesler, Elissa J. and Churchill, Gary A. and Villena, Fernando Pardo-Manuel and Kelada, Samir N. P.}, year={2014}, month={Oct}, pages={735–U376} }
 @article{kelada_carpenter_aylor_chines_rutledge_chesler_churchill_villena_schwartz_collins_2014, title={Integrative Genetic Analysis of Allergic Inflammation in the Murine Lung}, volume={51}, ISSN={["1535-4989"]}, DOI={10.1165/rcmb.2013-0501oc}, abstractNote={Airway allergen exposure induces inflammation among individuals with atopy that is characterized by altered airway gene expression, elevated levels of T helper type 2 cytokines, mucus hypersecretion, and airflow obstruction. To identify the genetic determinants of the airway allergen response, we employed a systems genetics approach. We applied a house dust mite mouse model of allergic airway disease to 151 incipient lines of the Collaborative Cross, a new mouse genetic reference population, and measured serum IgE, airway eosinophilia, and gene expression in the lung. Allergen-induced serum IgE and airway eosinophilia were not correlated. We detected quantitative trait loci (QTL) for airway eosinophilia on chromosome (Chr) 11 (71.802-87.098 megabases [Mb]) and allergen-induced IgE on Chr 4 (13.950-31.660 Mb). More than 4,500 genes expressed in the lung had gene expression QTL (eQTL), the majority of which were located near the gene itself. However, we also detected approximately 1,700 trans-eQTL, and many of these trans-eQTL clustered into two regions on Chr 2. We show that one of these loci (at 147.6 Mb) is associated with the expression of more than 100 genes, and, using bioinformatics resources, fine-map this locus to a 53 kb-long interval. We also use the gene expression and eQTL data to identify a candidate gene, Tlcd2, for the eosinophil QTL. Our results demonstrate that hallmark allergic airway disease phenotypes are associated with distinct genetic loci on Chrs 4 and 11, and that gene expression in the allergically inflamed lung is controlled by both cis and trans regulatory factors.}, number={3}, journal={AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY}, author={Kelada, Samir N. P. and Carpenter, Danielle E. and Aylor, David L. and Chines, Peter and Rutledge, Holly and Chesler, Elissa J. and Churchill, Gary A. and Villena, Fernando Pardo-Manuel and Schwartz, David A. and Collins, Francis S.}, year={2014}, month={Sep}, pages={436–445} }
 @article{xiao_ciavatta_aylor_hu_de villena_falk_jennette_2013, title={Genetically Determined Severity of Anti-Myeloperoxidase Glomerulonephritis}, volume={182}, ISSN={0002-9440}, url={http://dx.doi.org/10.1016/j.ajpath.2012.12.006}, DOI={10.1016/j.ajpath.2012.12.006}, abstractNote={Myeloperoxidase (MPO) is a target antigen for antineutrophil cytoplasmic autoantibodies (ANCA). There is evidence that MPO-ANCA cause necrotizing and crescentic glomerulonephritis (NCGN) and vasculitis. NCGN severity varies among patients with ANCA disease, and genetic factors influence disease severity. The role of genetics in MPO-ANCA NCGN severity was investigated using 13 inbred mouse strains, F1 and F2 hybrids, bone marrow chimeras, and neutrophil function assays. Mouse strains include founders of the Collaborative Cross. Intravenous injection of anti-MPO IgG induced glomerular crescents in >60% of glomeruli in 129S6/SvEv and CAST/EiJ mice, but <1% in A/J, DBA/1J, DBA/2J, NOD/LtJ, and PWK/PhJ mice. C57BL6J, 129S1/SvImJ, LP/J, WSB/EiJ, NZO/HILtJ, and C3H mice had intermediate severity. High-density genotypes at 542,190 single nucleotide polymorphisms were used to identify candidate loci for disease severity by identifying genomic regions that are different between 129S6/SvEv and 129S1/SvImJ mice, which are genetically similar but phenotypically distinct. C57BL/6 × 129S6 F2 mice were genotyped at 76 SNPs to capture quantitative trait loci for disease severity. The absence of a dominant quantitative trait locus suggests that differences in severity are the result of multiple gene interactions. In vivo studies using bone marrow chimeric mice and in vitro studies of neutrophil activation by anti-MPO IgG indicated that severity of NCGN is mediated by genetically determined differences in the function of neutrophils.}, number={4}, journal={The American Journal of Pathology}, publisher={Elsevier BV}, author={Xiao, Hong and Ciavatta, Dominic and Aylor, David L. and Hu, Peiqi and de Villena, Fernando Pardo-Manuel and Falk, Ronald J. and Jennette, J. Charles}, year={2013}, month={Apr}, pages={1219–1226} }
 @article{phillippi_xie_miller_bell_zhang_lenarcic_aylor_krovi_threadgill_pardo-manuel de villena_et al._2013, title={Using the emerging Collaborative Cross to probe the immune system}, volume={15}, ISSN={1466-4879 1476-5470}, url={http://dx.doi.org/10.1038/GENE.2013.59}, DOI={10.1038/GENE.2013.59}, abstractNote={The Collaborative Cross (CC) is an emerging panel of recombinant inbred (RI) mouse strains. Each strain is genetically distinct but all descended from the same eight inbred founders. In 66 strains from incipient lines of the CC (pre-CC), as well as the 8 CC founders and some of their F1 offspring, we examined subsets of lymphocytes and antigen-presenting cells. We found significant variation among the founders, with even greater diversity in the pre-CC. Genome-wide association using inferred haplotypes detected highly significant loci controlling B-to-T cell ratio, CD8 T-cell numbers, CD11c and CD23 expression. Comparison of overall strain effects in the CC founders with strain effects at QTL in the pre-CC revealed sharp contrasts in the genetic architecture of two traits with significant loci: variation in CD23 can be explained largely by additive genetics at one locus, whereas variation in B-to-T ratio has a more complex etiology. For CD23, we found a strong QTL whose confidence interval contained the CD23 structural gene Fcer2a. Our data on the pre-CC demonstrate the utility of the CC for studying immunophenotypes and the value of integrating founder, CC and F1 data. The extreme immunophenotypes observed could have pleiotropic effects in other CC experiments.}, number={1}, journal={Genes & Immunity}, publisher={Springer Science and Business Media LLC}, author={Phillippi, J and Xie, Y and Miller, D R and Bell, T A and Zhang, Z and Lenarcic, A B and Aylor, D L and Krovi, S H and Threadgill, D W and Pardo-Manuel de Villena, F and et al.}, year={2013}, month={Nov}, pages={38–46} }
 @article{mathes_aylor_miller_churchill_chesler_villena_threadgill_pomp_2011, title={Architecture of energy balance traits in emerging lines of the Collaborative Cross}, volume={300}, ISSN={["1522-1555"]}, DOI={10.1152/ajpendo.00707.2010}, abstractNote={The potential utility of the Collaborative Cross (CC) mouse resource was evaluated to better understand complex traits related to energy balance. A primary focus was to examine if genetic diversity in emerging CC lines (pre-CC) would translate into equivalent phenotypic diversity. Second, we mapped quantitative trait loci (QTL) for 15 metabolism- and exercise-related phenotypes in this population. We evaluated metabolic and voluntary exercise traits in 176 pre-CC lines, revealing phenotypic variation often exceeding that seen across the eight founder strains from which the pre-CC was derived. Many phenotypic correlations existing within the founder strains were no longer significant in the pre-CC population, potentially representing reduced linkage disequilibrium (LD) of regions harboring multiple genes with effects on energy balance or disruption of genetic structure of extant inbred strains with substantial shared ancestry. QTL mapping revealed five significant and eight suggestive QTL for body weight (Chr 4, 7.54 Mb; CI 3.32–10.34 Mb; Bwq14), body composition, wheel running (Chr 16, 33.2 Mb; CI 32.5–38.3 Mb), body weight change in response to exercise (1: Chr 6, 77.7Mb; CI 72.2–83.4 Mb and 2: Chr 6, 42.8 Mb; CI 39.4–48.1 Mb), and food intake during exercise (Chr 12, 85.1 Mb; CI 82.9–89.0 Mb). Some QTL overlapped with previously mapped QTL for similar traits, whereas other QTL appear to represent novel loci. These results suggest that the CC will be a powerful, high-precision tool for examining the genetic architecture of complex traits such as those involved in regulation of energy balance.}, number={6}, journal={AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM}, author={Mathes, Wendy Foulds and Aylor, David L. and Miller, Darla R. and Churchill, Gary A. and Chesler, Elissa J. and Villena, Fernando Pardo-Manuel and Threadgill, David W. and Pomp, Daniel}, year={2011}, month={Jun}, pages={E1124–E1134} }
 @article{aylor_zeng_2008, title={From classical genetics to quantitative genetics to systems biology: Modeling epistasis}, volume={4}, number={3}, journal={PLoS Genetics}, author={Aylor, D. L. and Zeng, Z. B.}, year={2008} }
 @article{zou_aylor_zeng_2007, title={eQTL Viewer: visualizing how sequence variation affects genome-wide transcription}, volume={8}, number={7}, journal={BMC Bioinformatics}, author={Zou, W. and Aylor, D. L. and Zeng, Z. B.}, year={2007} }