International Mammalian Genome Society

The 14th International Mouse Genome Conference (2000)

G12. QTL Mapping of Autoimmune Sialadenitis in NOD Mouse

Qian Chen1, Krista Condon1, Tatyana Sitnikova1, Hans Hansen1, Nanding Zhao1, Michelle Arya1, Sergei Agoulnik1, Mary Pat Reeve1, Andrew Kirby1, Masakazu Hattori2, and Hiroyuki Kato1
1 Eisai Research Institute of Boston, Inc.,100 Research Drive, Wilmington, MA 01887, U.S.A.
2 Joslin Diabetes Center, One Joslin Place, Boston, MA 02215, U.S.A.
Current Address: Eisai Research Institute of Boston, Inc., Four Corporate Drive, Andover, MA 01810, U.S.A.
Current Address: Laboratory of Seeds Finding Technology, Eisai Co., Ltd., 5-1-3 Tokodai, Tsukuba-shi, Ibaraki, 300-2635, Japan

The non-obese diabetic (NOD) mice develop histopathological changes and clinical manifestations similar to human Sjögren's syndrome. Therefore NOD mouse is recognized as a valuable animal model for studying pathogenesis of the Sjögren's syndrome. To map the susceptibility gene(s) for this disease in the NOD mouse, a whole genome scan for quantitative trait loci (QTL) specifying lymphocytic infiltration in the submandibular gland was performed using backcross 1 (BC1) [(NOD x Mus spretus) F1 x NOD] mice. Lymphocytic infiltration in the gland was examined in BC1 animals at 12-18 month of age. 145 genetic markers spanning all chromosomes, except Y, were analyzed with 116 BC1 mice. By interval mapping with MAPMAKER/QTL, we have identified multiple QTLs, which were associated with susceptibility to development of Sjögren's syndrome. One of them, Ss1, located on the middle part of chromosome (Chr) 7, is significantly associated with susceptibility to the incidence of lymphocytic infiltration (LOD = 3.30), and moderately associated with the severity of lymphocytic infiltration (LOD = 2.64). Several other genomic intervals on Chr 1 and Chr 5 showed suggestive linkages to either the incidence of lymphocytic infiltration or the severity of lymphocytic infiltration, or both. In addition, we have found three genomic intervals that were linked to heterozygosity of BC1 mice. The strongest one, Ss2, located on centromeric part of Chr 16, showed a significant association with both the incidence of lymphocytic infiltration (LOD = 5.21) and the severity of lymphocytic infiltration (LOD = 4.60). Analysis using composite interval mapping with QTL Cartographer confirmed above results for the severity of lymphocytic infiltration. Comparison of our mapped intervals to other murine autoimmune disease susceptibility loci revealed multiple overlapped regions that might be involved in general immune regulation.

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