| First Author | del Rio R | Year | 2012 |
| Journal | PLoS Genet | Volume | 8 |
| Issue | 12 | Pages | e1003140 |
| PubMed ID | 23300462 | Mgi Jnum | J:194925 |
| Mgi Id | MGI:5475064 | Doi | 10.1371/journal.pgen.1003140 |
| Citation | del Rio R, et al. (2012) Identification of Orch3, a locus controlling dominant resistance to autoimmune orchitis, as kinesin family member 1C. PLoS Genet 8(12):e1003140 |
| abstractText | 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 Kif1c(D2) 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 L(578) --> P(578) and S(1027) --> P(1027) 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. |
