International Mammalian Genome Society

The 15th International Mouse Genome Conference (2001)



POSTER 26 - A MAJOR DETERMINANT QTL RESPONSIBLE FOR ATOPIC DERMATITIS-LIKE SKIN LESIONS IN NC/Nga IS LOCATED CHOROMOSOME 9

Dr. Yuki Kohara
The Tokyo Metropolitan Institute of Medical Science
3-18-22, Honkomagome, Bunkyo-ku Tokyo 113-8613, JAPAN

Co-Authors: 1)Kohara Y, 1)Tanabe K,  1)Matsuoka K, 2)Kanda N, 2)Matsuda H,  3)Karasuyama H, 1)Yonekawa H
Institutions: 1) Department of Laboratory Animal Science, The Tokyo Metropolitan Institute of Medical Science, 2) Department of Veterinary Medicine, Tokyo University of Agriculture and Technology, 3)Department of Immune Regulation Tokyo Medical and Dental University

NC/Nga (NC) is a newly discovered model mouse for human atopic dermatitis, NC mice showing specific symptoms such as dermatitis and overproduction of IgE. To detect the loci responsible for the onset of dermatitis in the mice, backcross (N2) progeny between (NCxMSM/MS)F1 and NC were generated, where MSM/MS is an inbred strain from Japanese wild mice, Mus musculus molossinus. Linkage disequilibrium between dermatitis and various chromosome-specific microsatellite markers was then examined in the N2 segregants with severe dermatitis. The analysis revealed that the locus of the major determinant (designated here as derm1) was tightly linked to D9Mit163, D9Mit72, D9Mit143, D9Mit103, D9Mit207, and D9Mit209, because these markers showed the highest and most significant chi2 values. Since no recombination was observed among the markers in our linkage map, a radiation hybrid (RH) panel was applied to locate the derm1 locus more precisely. The markers were separated on the RH map, and their order was D9Mit163-D9Mit72-D9Mit143-D9Mit103-D9Mit207-D9Mit209 from the centromere. Several functional candidate genes are located near the locus derm1. These candidates are Thy1, Cd3d, Cd3e, Cd3g, Il10ra, Il18, and Csk, all of which could be involved in allergic responses through effects on T-cell function. Of these candidates, Csk is the strongest for NC dermatitis, since its map position was most tightly linked to the derm1 locus.


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