Boackle S A, Holers V M, Chen X, Szakonyi G, Karp D R, Wakeland E K, Morel L
Department of Medicine, University of Colorado Health Sciences Center, Denver, CO 80262, USA.
Immunity. 2001 Nov;15(5):775-85. doi: 10.1016/s1074-7613(01)00228-x.
The major murine systemic lupus erythematosus (SLE) susceptibility locus, Sle1, corresponds to three loci independently affecting loss of tolerance to chromatin in the NZM2410 mouse. The congenic interval corresponding to Sle1c contains Cr2, which encodes complement receptors 1 and 2 (CR1/CR2, CD35/CD21). NZM2410/NZW Cr2 exhibits a single nucleotide polymorphism that introduces a novel glycosylation site, resulting in higher molecular weight proteins. This polymorphism, located in the C3d binding domain, reduces ligand binding and receptor-mediated cell signaling. Molecular modeling based on the recently solved CR2 structure in complex with C3d reveals that this glycosylation interferes with receptor dimerization. These data demonstrate a functionally significant phenotype for the NZM2410 Cr2 allele and strongly support its role as a lupus susceptibility gene.
主要的小鼠系统性红斑狼疮（SLE）易感基因座Sle1，对应于三个独立影响NZM2410小鼠对染色质耐受性丧失的基因座。与Sle1c相对应的同源区间包含Cr2，它编码补体受体1和2（CR1/CR2，CD35/CD21）。NZM2410/NZW Cr2表现出一种单核苷酸多态性，该多态性引入了一个新的糖基化位点，导致分子量更高的蛋白质。这种位于C3d结合域的多态性降低了配体结合和受体介导的细胞信号传导。基于最近解析的与C3d复合的CR2结构进行的分子建模表明，这种糖基化会干扰受体二聚化。这些数据证明了NZM2410 Cr2等位基因具有功能上显著的表型，并有力地支持了其作为狼疮易感基因的作用。
