A major determinant quantitative-trait locus responsible for atonic dermatitis-like skin lesions in NC/Nga mice is located on Chromosome 9
A major determinant quantitative-trait locus responsible for atonic dermatitis-like skin lesions in NC/Nga mice is located on Chromosome 9
复制标题
DOI：
10.1007/s002510000286
复制
发表时间：
2001-02-01
期刊：
影响因子：
3.2
通讯作者：
Yonekawa, H
中科院分区：
文献类型：
--
作者：
Kohara, Y;Tanabe, K;Yonekawa, H
NC/NGA(NC)是一种新发现的人类特应性皮炎模型小鼠，NC小鼠表现出皮炎、IgE分泌过多等特异性症状。为了检测小鼠皮炎发病的基因座，在(NCxMSM/MS)F1和NC之间产生回交(N2)后代，其中msm/MS是来自日本野鼠的近交系。然后，在患有严重皮炎的N_2分离物中，研究皮炎与各种染色体特异性微卫星标记之间的连锁不平衡。分析表明，D9Mit163、D9Mit72、D9Mit143、D9Mit103、D9Mit207和D9Mit209与主要决定基因D9Mit163、D9Mit72、D9Mit143、D9Mit207和D9Mit209紧密连锁，因为这些标记具有最高和最显著的chi(2)值。由于我们的连锁图谱中没有观察到标记之间的重组，因此应用辐射杂交(RH)面板来更准确地定位derm1基因座。这些标记在RH图谱上是分离的，其顺序为D9Mit163-D9Mit72-D9Mit143D9Mit103-D9Mit207-D9Mit209和着丝粒。几个功能候选基因位于derm1位点附近。这些候选基因是Thy1、Cd3d、Cd3e、Cd3g、Il10ra、Il18和CSK，它们都可能通过影响T细胞功能而参与过敏反应。在这些候选基因中，CSK对NC皮炎的作用最强，因为它的MAP位置与derm1基因联系最紧密。
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 chi (2) 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-D9Mit143D9Mit103-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.