Identification of Orch3, a locus controlling dominant resistance to autoimmune orchitis, as kinesin family member 1C.
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 gen...
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doaj-21ac66638c804c51aade9d4bd5ec27fa2020-11-24T22:19:26ZengPublic Library of Science (PLoS)PLoS Genetics1553-73901553-74042012-01-01812e100314010.1371/journal.pgen.1003140Identification of Orch3, a locus controlling dominant resistance to autoimmune orchitis, as kinesin family member 1C.Roxana del RioRyan D McAllisterNathan D MeekerEmma H WallJeffrey P BondVasileios C KyttarisGeorge C TsokosKenneth S K TungCory TeuscherExperimental 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.http://europepmc.org/articles/PMC3531464?pdf=render |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Roxana del Rio Ryan D McAllister Nathan D Meeker Emma H Wall Jeffrey P Bond Vasileios C Kyttaris George C Tsokos Kenneth S K Tung Cory Teuscher |
spellingShingle |
Roxana del Rio Ryan D McAllister Nathan D Meeker Emma H Wall Jeffrey P Bond Vasileios C Kyttaris George C Tsokos Kenneth S K Tung Cory Teuscher Identification of Orch3, a locus controlling dominant resistance to autoimmune orchitis, as kinesin family member 1C. PLoS Genetics |
author_facet |
Roxana del Rio Ryan D McAllister Nathan D Meeker Emma H Wall Jeffrey P Bond Vasileios C Kyttaris George C Tsokos Kenneth S K Tung Cory Teuscher |
author_sort |
Roxana del Rio |
title |
Identification of Orch3, a locus controlling dominant resistance to autoimmune orchitis, as kinesin family member 1C. |
title_short |
Identification of Orch3, a locus controlling dominant resistance to autoimmune orchitis, as kinesin family member 1C. |
title_full |
Identification of Orch3, a locus controlling dominant resistance to autoimmune orchitis, as kinesin family member 1C. |
title_fullStr |
Identification of Orch3, a locus controlling dominant resistance to autoimmune orchitis, as kinesin family member 1C. |
title_full_unstemmed |
Identification of Orch3, a locus controlling dominant resistance to autoimmune orchitis, as kinesin family member 1C. |
title_sort |
identification of orch3, a locus controlling dominant resistance to autoimmune orchitis, as kinesin family member 1c. |
publisher |
Public Library of Science (PLoS) |
series |
PLoS Genetics |
issn |
1553-7390 1553-7404 |
publishDate |
2012-01-01 |
description |
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. |
url |
http://europepmc.org/articles/PMC3531464?pdf=render |
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