Analysis of the mouse CD30 gene - A candidate for the NOD mouse type 1 diabetes locus Idd9.2

Members of the tumor necrosis factor receptor superfamily play an important role in the initiation, expansion, and termination of an immune response. It has recently been demonstrated that one member of this family, CD30, pla ys a central role in maintaining peripheral tolerance by controlling the ex pansion of autoreactive CD8(+)T-cells, In the present study, Cd30 was mappe d to a 5.6-cM interval on chromosome 4 containing the type I diabetes susce ptibility locus Idd9.2. We determined the intron/exon structure of Cd30 and sequenced the exons, as well as 1.8 kb of the 5' putative promoter region, from 6 different mouse strains. Remarkably, 63 sequence variants, both cod ing and noncoding, were found. A total of 27 sequence variants, 4 of which were nonsynonymous, were found between the diabetes susceptible NOD strain and the resistant B10 strain. Of these sequence variants, 19 are within the promoter region. However, no difference between NOD and the congenic strai n NOD,B10 Idd9R1, which has the B10 allele of Cd30, was observed in CD30 ex pression at either the mRNA or protein level. Given its role in protecting against autoimmunity, one or more of the coding variants within CD30 is a g ood candidate for the Idd9.2 etiological variant.