Lrmp and Bcat1 are candidates for the type I diabetes susceptibility locus Idd6.
Three type 1 diabetes associated regions on distal mouse chromosome 6 have recently been defined by the construction and analysis of a series of congenic strains, carrying C3H/HeJ genomic material on a NOD/Lt genetic background. Whilst NOD/Lt alleles at the most distal locus Idd6 confer susceptibility, C3H/HeJ alleles confer resistance to diabetes. Idd6 overlaps with a locus controlling low rates of proliferation in immature NOD-thymocytes, suggesting that Idd6 could be controlling diabetes development through an effect on T cell proliferation rates. Candidates for Idd6 therefore include genes, which are implicated in the immune system and/or in the control of cell proliferation rates, such as Lrmp (Jaw1), Bcat1 and Kras2 that map to the Idd6 candidate region. In the present study, we have undertaken an expression and mutational analysis of all three genes. A surprisingly large number of polymorphisms and amino acid changes were identified in both Lrmp and Bcat1 indicating that they are candidates for Idd6. The two genes are located within a genomic interval of about 3 Mb that contains a large number of single nucleotide polymorphisms (SNP) and which has possibly been derived from distinct ancestral haplotypes in the C3H/HeJ and NOD/Lt strains.
Grimm
Christina H
CH
Unité de Génétique Moléculaire Murine, Institut Pasteur 25 rue du Docteur Roux, F-75724, Paris Cedex 15, France.
Rogner
Ute C
UC
Avner
Philip
P
D000818:Animals; D002874:Chromosome Mapping; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics* / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D016688:Mice, Inbred NOD; D020641:Polymorphism, Single Nucleotide; D011506:Proteins / Q000235:genetics* / Q000276:immunology*; D012313:RNA / Q000737:chemistry / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017422:Sequence Analysis, DNA; D000637:Transaminases
C486311:IRAG2 protein, human; C101764:Lrmp protein, mouse; D008565:Membrane Proteins; D011506:Proteins; D012313:RNA; C490590:BCAT1 protein, human; C094227:Bcat1 protein, mouse; D000637:Transaminases