A major determinant quantitative-trait locus responsible for atonic dermatitis-like skin lesions in NC/Nga mice is located on Chromosome 9

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 molossinu s. Linkage disequilibrium between dermatitis and various chromosome-specifi c 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, D9Mit14 3, D9Mit103, D9Mit207, and D9Mit209, because these markers showed the highe st and most significant chi (2) values. Since no recombination was observed among the markers in our linkage map, a radiation hybrid (RH) panel was ap plied to locate the derm1 locus more precisely. The markers were separated on the RH map, and their order was D9Mit163-D9Mit72-D9Mit143D9Mit103-D9Mit2 07-D9Mit209 from the centromere. Several functional candidate genes are loc ated near the locus derm1. These candidates are Thy1, Cd3d, Cd3e, Cd3g, Il1 0ra, Il18, and Csk, all of which could be involved in allergic responses th rough 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 d erm1 locus.