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目的 :定位NZB、NZW及NZB WF1小鼠外周血B1细胞增殖的易感基因。方法 :建立 (NZB×NZW )F1×NZB回交小鼠模型 ,用覆盖小鼠全部常染色体的多态性微卫星遗传标记数量性状位点 (QTL)分析进行基因定位。结果 :B1细胞增殖的易感基因与小鼠的第 2、4、17号染色体上的微卫星遗传标记D2Mit 10 1、D4Mit 11及D17Mit 6 1肯定连锁 (Lods值 >3) ,其中D2Mit10 1、D4Mit11位点来源于NZB ,D17Mit 6 1位点来源于NZW。在D2Mit10 1位点附近存在Ltk、Rag1、2基因 ,在D4Mit 11位点附近存在Lck基因 ,在D17Mit6 1位点附近存在H 2及TNF α基因。结论 :NZB、NZW及NZB WF1小鼠外周血B1细胞增殖受多基因调控 ,易感基因分别位于NZB的Ltk、Rag1、2及Lck基因编码区和位于NZW的H 2、TNF α基因编码区 ,这些易感基因之间有相互促进的叠加效应。
OBJECTIVE: To locate the susceptibility genes of peripheral blood B1 cell proliferation in NZB, NZW and NZB WF1 mice. Methods: A (NZB × NZW) F1 × NZB backcross mouse model was established and the gene mapping was performed by using QTL analysis of the polymorphic microsatellite markers covering all the autosomes in mice. RESULTS: The susceptibility genes of B1 cell proliferation were positively linked to the microsatellite markers D2Mit 10 1, D4Mit 11 and D17Mit 6 1 on chromosomes 2, 4 and 17 (Lods value> 3). Among them, D2Mit10 1, The D4Mit11 site is derived from NZB and the D17Mit 6 1 site is derived from NZW. There are Ltk and Rag1,2 genes in the vicinity of the D2Mit10 1 locus, Lck gene in the vicinity of the D4Mit 11 locus and H2 and TNFα genes in the vicinity of the D17Mit61 locus. CONCLUSION: The proliferation of B1 cells in peripheral blood of NZB, NZW and NZB WF1 mice is regulated by multiple genes. The susceptible genes are located in the coding region of Ltk, Rag1, 2 and Lck of NZB and the coding region of H2 and TNF α of NZW in NZW respectively. There is a mutually reinforcing additive effect between these susceptible genes.