@article{jima_shah_orcutt_joshi_law_litman_trede_yoder_2009, title={Enhanced transcription of complement and coagulation genes in the absence of adaptive immunity}, volume={46}, ISSN={0161-5890}, url={http://dx.doi.org/10.1016/j.molimm.2008.12.021}, DOI={10.1016/j.molimm.2008.12.021}, abstractNote={A recessive nonsense mutation in the zebrafish recombination activating gene 1 (rag1) gene results in defective V(D)J recombination; however, animals homozygous for this mutation (rag1(-/-)) are reportedly viable and fertile in standard, nonsterile aquarium conditions but display increased mortality after intraperitoneal injection with mycobacteria. Based on their survival in nonsterile environments, we hypothesized that the rag1(-/-) zebrafish may possess an "enhanced" innate immune response to compensate for the lack of an adaptive immune system. To test this hypothesis, microarray analyses were used to compare the expression profiles of the intestines and hematopoietic kidneys of rag1 deficient zebrafish to the expression profiles of control (heterozygous) siblings. The expression levels of 12 genes were significantly altered in the rag1(-/-) kidney including the up regulation of a putative interferon stimulated gene, and the down regulation of genes encoding fatty acid binding protein 10, keratin 5 and multiple heat shock proteins. The expression levels of 87 genes were shown to be significantly altered in the rag1(-/-) intestine; the majority of these differences reflect increased expression of innate immune genes, including those of the coagulation and complement pathways. Subsequent analyses of orthologous coagulation and complement genes in Rag1(-/-) mice indicate increased transcription of the complement C4 gene in the Rag1(-/-) intestine.}, number={7}, journal={Molecular Immunology}, publisher={Elsevier BV}, author={Jima, Dereje D. and Shah, Radhika N. and Orcutt, Timothy M. and Joshi, Deepa and Law, J. McHugh and Litman, Gary W. and Trede, Nikolaus S. and Yoder, Jeffrey A.}, year={2009}, month={Apr}, pages={1505–1516} }
 @article{desai_heffelfinger_orcutt_litman_yoder_2008, title={The medaka novel immune-type receptor (NITR) gene clusters reveal an extraordinary degree of divergence in variable domains}, volume={8}, ISSN={1471-2148}, url={http://dx.doi.org/10.1186/1471-2148-8-177}, DOI={10.1186/1471-2148-8-177}, abstractNote={Abstract
          
            Background
            Novel immune-type receptor (NITR) genes are members of diversified multigene families that are found in bony fish and encode type I transmembrane proteins containing one or two extracellular immunoglobulin (Ig) domains. The majority of NITRs can be classified as inhibitory receptors that possess cytoplasmic immunoreceptor tyrosine-based inhibition motifs (ITIMs). A much smaller number of NITRs can be classified as activating receptors by the lack of cytoplasmic ITIMs and presence of a positively charged residue within their transmembrane domain, which permits partnering with an activating adaptor protein.
          
          
            Results
            Forty-four NITR genes in medaka (Oryzias latipes) are located in three gene clusters on chromosomes 10, 18 and 21 and can be organized into 24 families including inhibitory and activating forms. The particularly large dataset acquired in medaka makes direct comparison possible to another complete dataset acquired in zebrafish in which NITRs are localized in two clusters on different chromosomes. The two largest medaka NITR gene clusters share conserved synteny with the two zebrafish NITR gene clusters. Shared synteny between NITRs and CD8A/CD8B is limited but consistent with a potential common ancestry.
          
          
            Conclusion
            Comprehensive phylogenetic analyses between the complete datasets of NITRs from medaka and zebrafish indicate multiple species-specific expansions of different families of NITRs. The patterns of sequence variation among gene family members are consistent with recent birth-and-death events. Similar effects have been observed with mammalian immunoglobulin (Ig), T cell antigen receptor (TCR) and killer cell immunoglobulin-like receptor (KIR) genes. NITRs likely diverged along an independent pathway from that of the somatically rearranging antigen binding receptors but have undergone parallel evolution of V family diversity.
          }, number={1}, journal={BMC Evolutionary Biology}, publisher={Springer Nature}, author={Desai, Salil and Heffelfinger, Amy K and Orcutt, Timothy M and Litman, Gary W and Yoder, Jeffrey A}, year={2008}, pages={177} }
 @article{yoder_orcutt_traver_litman_2007, title={Structural characteristics of zebrafish orthologs of adaptor molecules that associate with transmembrane immune receptors}, volume={401}, ISSN={0378-1119}, url={http://dx.doi.org/10.1016/j.gene.2007.07.014}, DOI={10.1016/j.gene.2007.07.014}, abstractNote={Transmembrane bound receptors comprised of extracellular immunoglobulin (Ig) or lectin domains play integral roles in a large number of immune functions including inhibitory and activating responses. The function of many of the activating receptors requires a physical interaction with an adaptor protein possessing a cytoplasmic regulatory motif. The partnering of an activating receptor with an adaptor protein relies on complementary charged residues in the two transmembrane domains. The mammalian natural killer (NK) and Fc receptors (FcR) represent two of many receptor families, which possess activating receptors that partner with adaptor proteins for signaling. Zebrafish represent a powerful experimental model for understanding developmental regulation at early stages of embryogenesis and for efficiently generating transgenic animals. In an effort to understand developmental aspects of immune receptor function, we have accessed the partially annotated zebrafish genome to identify six different adaptor molecules: Dap10, Dap12, Cd3ζ, Cd3ζ-like, FcRγ and FcRγ-like that are homologous to those effecting immune function in mammals. Their genomic organizations have been characterized, cDNA transcripts have been recovered, phylogenetic relationships have been defined and their cell lineage-specific expression patterns have been established.}, number={1-2}, journal={Gene}, publisher={Elsevier BV}, author={Yoder, Jeffrey A. and Orcutt, Timothy M. and Traver, David and Litman, Gary W.}, year={2007}, month={Oct}, pages={154–164} }
 @article{wei_zhou_chen_shah_liu_orcutt_traver_djeu_litman_yoder_et al._2007, title={The zebrafish activating immune receptor Nitr9 signals via Dap12}, volume={59}, ISSN={0093-7711 1432-1211}, url={http://dx.doi.org/10.1007/s00251-007-0250-6}, DOI={10.1007/s00251-007-0250-6}, abstractNote={Both inhibitory and activating forms of natural killer (NK) cell receptors are found in mammals. The activating receptors play a direct role in the recognition of virally infected or transformed cells and transduce activating signals into the cell by partnering with an adaptor protein, which contains a cytoplasmic activation motif. Activating NK receptors encoded by the mammalian leukocyte receptor complex (e.g., killer cell immunoglobulin-like receptors) and the natural killer complex (e.g., Ly49s) partner with the adaptor protein DAP12, whereas NK receptors encoded in the CD94/NKG2 complex partner with the adaptor protein DAP10. Novel immune-type receptors (NITRs) found in bony fish share several common features with immunoglobulin-type NK receptors. Nitr9 is a putative activating receptor in zebrafish that induces cytotoxicity within the context of human NK cells. One isoform of Nitr9, Nitr9L, is shown here to preferentially partner with a zebrafish ortholog of Dap12. Cross-linking the Nitr9L–Dap12 complex results in activation of the phosphytidylinositol 3-kinase→AKT→extracellular signal-regulated kinase pathway suggesting that the DAP12-based activating pathway is conserved between bony fish and mammals.}, number={10}, journal={Immunogenetics}, publisher={Springer Science and Business Media LLC}, author={Wei, S. and Zhou, J.-M. and Chen, X. and Shah, R.N. and Liu, J. and Orcutt, T.M. and Traver, D. and Djeu, J.Y. and Litman, G.W. and Yoder, Jeffrey and et al.}, year={2007}, month={Sep}, pages={813–821} }