Santiago M L, Mary C, Parzy D, Jacquet C, Montagutelli X, Parkhouse R M, Lemoine R, Izui S, Reininger L
INSERM U399, Université de la Méditerranée, Marseille, France.
Eur J Immunol. 1998 Dec;28(12):4257-67. doi: 10.1002/(SICI)1521-4141(199812)28:12<4257::AID-IMMU4257>3.0.CO;2-H.
In the present study, we mapped the major quantitative trait loci (QTL) differing between the NZW and C57BL/6 inbred strains of mice by making use of (NZW x C57BL/6.Yaa)F1 mice, a model in which the lupus-like autoimmune syndrome observed in male mice is associated with the presence of an as yet unidentified Y chromosome-linked autoimmune acceleration gene, Yaa. Linkage analysis of 126 C57BL/6 x (NZW x C57BL/6.Yaa)F1 backcross males provided evidence for a major QTL on chromosome 7 controlling both the severity of glomerulonephritis and the production of IgG anti-DNA autoantibody and retroviral gp70-anti-gp70 immune complexes. Two additional QTL of C57BL/6 origin on chromosome 17 had no apparent individual effects, but showed strong epistatic interaction with chromosome 7 QTL for disease severity and anti-DNA autoantibody production. Our data also identified on chromosome 13 a QTL of NZW origin with a major effect on the level of gp70, and showing an additive effect with the chromosome 7 QTL on the level of gp70 immune complexes. Our study thus provides a model to dissect the complex genetic interactions that result in manifestations of murine lupus-like disease.
在本研究中，我们利用（新西兰白兔×C57BL/6.Yaa）F1小鼠绘制了新西兰白兔（NZW）和C57BL/6近交系小鼠之间存在差异的主要数量性状位点（QTL）图谱。在该模型中，雄性小鼠中观察到的狼疮样自身免疫综合征与一个尚未确定的Y染色体连锁自身免疫加速基因Yaa的存在有关。对126只C57BL/6×（新西兰白兔×C57BL/6.Yaa）F1回交雄性小鼠进行连锁分析，结果表明7号染色体上存在一个主要QTL，它控制着肾小球肾炎的严重程度以及IgG抗DNA自身抗体和逆转录病毒gp70-抗gp70免疫复合物的产生。17号染色体上另外两个源自C57BL/6的QTL没有明显的个体效应，但在疾病严重程度和抗DNA自身抗体产生方面与7号染色体QTL表现出强烈的上位性相互作用。我们的数据还在13号染色体上鉴定出一个源自新西兰白兔的QTL，它对gp70水平有主要影响，并且在gp70免疫复合物水平上与7号染色体QTL表现出加性效应。因此，我们的研究提供了一个模型，用于剖析导致小鼠狼疮样疾病表现的复杂遗传相互作用。
