Experiment
Susceptibility loci for autoimmune exocrinopathy (Aec1 and Aec2) previously mapped to mouse Chromosomes 3 and 1 overlapping with diabetes susceptibility loci Idd3 and Idd5, respectively.
The Aec1 locus extends from the centromere (D3Mit164) to 48.5 cM (Tshb) on chromosome 3. Authors studied Sjogren syndrome-like exocrinopathy phenotypes in a susceptible double congenic mouse line (B6.NOD-Aec2NOD/Uf Aec1NOD/Uf) in which recombination had occurred within the Aec1 (autoimmune exocrinopathy 1) at 19.5 cM near D3Mit151. This new line is referred to as B6.NOD-Aec2NOD/Uf Aec1R1NOD/Uf and carries NOD/Uf-derived DNA from the chromosome 3 centromere to 19.5 cM for Aec1 and from 32 cM (D1Mit18) to 101 cM (D1Mit360) for Aec2 on chromosome 1 on a C57BL/6J genetic background.
The subcongenic line displays lacrimal and salivary gland pathology similar to the original congenic line. Subcongenic animals develop sialadenitis by 10 weeks of age in males and by 19 weeks of age in females, with a more severe phenotype in the females. Both sexes display a 35-40% reduction in salivary flow rate at age 5-19 weeks for males and age 5-22 weeks for females. Salivary amylase activity also showed significant decline by age 19-22 weeks in both sexes. Interestingly, males develop severe lacrimal gland inflammation and loss of secretory function where as females do not. Anti-nuclear antibody production was present in male subcongenic animals as early as age 5 weeks but was not present in female subcongenic animals until age 10 weeks.
Il2 (19.2 cM, chr3) is an attractive candidate gene for Aec1. This gene is located near the recombination breakpoint and is associated with susceptibility to autoimmune diseases, such as ulcerative colitis and rheumatoid arthritis. Other potential candidate genes in the Aec1 interval include Il7 (6.6 cM), Car1 (10.5 cM), Car2 (10.5 cM), Car3 (11.7 cM), Gpr177 (formerly Evi, 14.4 cM), Fim3 (14.4 cM), Mpmv20 (13.8 cM), Mtv56 (7.5 cM), and Pad4 (10 cM).