{"corpus_id":18289493,"paper_sha":"7531c517621389e7206d0cb2bf7e0659a61bf555","doi":"10.1371/journal.pgen.1003140","arxiv_id":null,"pmid":23300462,"pmcid":"3531464","mag_id":2098104119,"dblp_id":null,"acl_id":null,"title":"Identification of Orch3, a Locus Controlling Dominant Resistance to Autoimmune Orchitis, as Kinesin Family Member 1C","year":2012,"publication_date":"2012-12-01","venue":"PLoS Genetics","journal":{"name":"PLoS Genetics","pages":null,"volume":"8"},"journal_issn":null,"journal_title":null,"publication_types":["JournalArticle"],"pubmed_pub_types":["Journal Article","Research Support, N.I.H., Extramural"],"s2_fields_of_study":["Biology","Medicine"],"reference_count":60,"citation_count":17,"influential_citation_count":0,"is_open_access":true,"arxiv_categories":null,"arxiv_license":null,"arxiv_journal_ref":null,"mesh_headings":[{"d":"Alleles","mj":false,"ui":"D000483"},{"d":"Animals","mj":false,"ui":"D000818"},{"d":"Autoimmune Diseases","mj":false,"qs":[{"q":"genetics","mj":false,"ui":"Q000235"},{"q":"immunology","mj":false,"ui":"Q000276"}],"ui":"D001327"},{"d":"Disease Resistance","mj":false,"qs":[{"q":"genetics","mj":true,"ui":"Q000235"}],"ui":"D060467"},{"d":"Gene Expression","mj":false,"ui":"D015870"},{"d":"Genes, Dominant","mj":true,"ui":"D005799"},{"d":"Genes, MHC Class II","mj":false,"ui":"D005802"},{"d":"Genetic Predisposition to Disease","mj":false,"ui":"D020022"},{"d":"Humans","mj":false,"ui":"D006801"},{"d":"Kinesins","mj":false,"qs":[{"q":"genetics","mj":true,"ui":"Q000235"}],"ui":"D016547"},{"d":"Male","mj":false,"ui":"D008297"},{"d":"Mice","mj":false,"ui":"D051379"},{"d":"Mice, Inbred BALB C","mj":false,"ui":"D008807"},{"d":"Mice, Inbred DBA","mj":false,"ui":"D008811"},{"d":"Orchitis","mj":true,"qs":[{"q":"genetics","mj":false,"ui":"Q000235"},{"q":"immunology","mj":false,"ui":"Q000276"}],"ui":"D009920"},{"d":"Quantitative Trait Loci","mj":false,"qs":[{"q":"genetics","mj":false,"ui":"Q000235"}],"ui":"D040641"},{"d":"Testis","mj":false,"qs":[{"q":"immunology","mj":false,"ui":"Q000276"}],"ui":"D013737"}],"chemicals":[{"n":"Kif1c protein, mouse","ui":"C485246","reg":"0"},{"n":"Kinesins","ui":"D016547","reg":"EC 3.6.4.4"}],"comments_corrections":null,"source_flags":5,"s2_open_access_pdf_url":"https://journals.plos.org/plosgenetics/article/file?id=10.1371/journal.pgen.1003140&type=printable","s2_open_access_landing_url":"https://www.semanticscholar.org/paper/7531c517621389e7206d0cb2bf7e0659a61bf555","s2_open_access_license":"CCBY","s2_open_access_status":"GOLD","pmc_open_access_pdf_url":null,"pmc_open_access_landing_url":null,"pmc_open_access_license":null,"pmc_open_access_status":null,"unpaywall_open_access_pdf_url":null,"unpaywall_open_access_landing_url":null,"unpaywall_open_access_license":null,"unpaywall_open_access_status":null,"abstract":"Experimental autoimmune orchitis (EAO), the principal model of non-infectious testicular inflammatory disease, can be induced in susceptible mouse strains by immunization with autologous testicular homogenate and appropriate adjuvants. As previously established, the genome of DBA/2J mice encodes genes that are capable of conferring dominant resistance to EAO, while the genome of BALB/cByJ mice does not and they are therefore susceptible to EAO. In a genome scan, we previously identified Orch3 as the major quantitative trait locus controlling dominant resistance to EAO and mapped it to chromosome 11. Here, by utilizing a forward genetic approach, we identified kinesin family member 1C (Kif1c) as a positional candidate for Orch3 and, using a transgenic approach, demonstrated that Kif1c is Orch3. Mechanistically, we showed that the resistant Kif1cD2 allele leads to a reduced antigen-specific T cell proliferative response as a consequence of decreased MHC class II expression by antigen presenting cells, and that the L578→P578 and S1027→P1027 polymorphisms distinguishing the BALB/cByJ and DBA/2J alleles, respectively, can play a role in transcriptional regulation. These findings may provide mechanistic insight into how polymorphism in other kinesins such as KIF21B and KIF5A influence susceptibility and resistance to human autoimmune diseases.","claims":[{"public_id":"cl_91ec9bbc2c286eb11fd5039e0b2ece2f","status":"active","text":"Kif1c is the gene underlying Orch3, the major quantitative trait locus controlling dominant resistance to experimental autoimmune orchitis.","confidence":0.98,"contributors":[{"id":1,"public_id":"12632b8b5f","public_label":"Anonymous (12632b8b5f)","roles":["extraction"],"url":"https://sah.borca.ai/u/12632b8b5f"}],"url":"https://sah.borca.ai/claims/cl_91ec9bbc2c286eb11fd5039e0b2ece2f"},{"public_id":"cl_9c1c70945d718e3f4db4f076a09451e3","status":"active","text":"The L578→P578 and S1027→P1027 polymorphisms that distinguish the BALB/cByJ and DBA/2J alleles may contribute to transcriptional regulation.","confidence":0.88,"contributors":[{"id":1,"public_id":"12632b8b5f","public_label":"Anonymous 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proline at position 1027 distinguishing the BALB/cByJ and DBA/2J Kif1c alleles.","types":["genetic variant"],"aliases":[],"contributors":[{"id":1,"public_id":"12632b8b5f","public_label":"Anonymous (12632b8b5f)","roles":["extraction"],"url":"https://sah.borca.ai/u/12632b8b5f"}],"url":"https://sah.borca.ai/concepts/co_973aefb6123a20c0be5b320c23f5f75b"},{"public_id":"co_b2af3ae0a65f42e8dadc2a7d7a2be5ed","status":"active","name":"dominant resistance to experimental autoimmune orchitis","description":"A genetically controlled resistance phenotype to experimental autoimmune orchitis that is inherited in a dominant manner.","types":["phenotype"],"aliases":["dominant resistance to EAO"],"contributors":[{"id":1,"public_id":"12632b8b5f","public_label":"Anonymous 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