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新西兰小鼠自身免疫的遗传学研究。IV. NZB和NZW基因对(NZB×NZW)F1杂种中逆转录病毒gp70免疫复合物自发出现的贡献及其与肾脏疾病的相关性。

Genetic studies of autoimmunity in New Zealand mice. IV. Contribution of NZB and NZW genes to the spontaneous occurrence of retroviral gp70 immune complexes in (NZB X NZW)F1 hybrid and the correlation to renal disease.

作者信息

Maruyama N, Furukawa F, Nakai Y, Sasaki Y, Ohta K, Ozaki S, Hirose S, Shirai T

出版信息

J Immunol. 1983 Feb;130(2):740-6.

PMID:6217253
Abstract

We designed a polyethylene glycol precipitation method for detecting retroviral gp70-anti-gp70 immune complexes (gp70 IC) in the circulation of mice. To determine the genetic contribution of NZB and NZW strains to the spontaneous occurrence of circulating gp70 IC in NZB X NZW (B/W)F1 hybrids, we measured these IC in female NZB, NZW, (NZB X NZW)F1 (B/W F1), B/W F1 X NZW backcross, and B/W F1 X NZB backcross mice. The highest amounts of gp70 IC were found in B/W F1 and the lowest in NZW mice, and the order of the average serum levels was B/W F1, B/W F1 X NZB, B/W F1 X NZW, NZB, and NZW. Genetic analyses suggested that two major dominant genes, one from NZB and the other from NZW, are involved in the formation of these gp70 IC. A single dominant gene of NZB strain determines the formation of these IC, and the magnitude is to a great degree modified (intensified) by the NZW gene. In addition, statistical analyses of data obtained in the studies of B/W F1 X NZW backcrosses suggested the presence of one additional dominant NZB gene that also regulates the magnitude of gp70 IC formation in concert with the other NZB gene. Since all these New Zealand mice share a high serum level of free gp70, the formation of gp70 IC represents the gene action on the production of anti-gp70 antibodies. Linkage studies showed that both of the major NZB and NZW genes are loosely linked to the H-2 complex but not to either the Mup-1 or coat color gene loci examined. The incidence of proteinuria correlated well with the serum level of gp70 IC in both B/W F1 X NZW and B/W F1 X NZB backcross mice.

摘要

我们设计了一种聚乙二醇沉淀法,用于检测小鼠循环系统中的逆转录病毒gp70 - 抗gp70免疫复合物(gp70 IC)。为了确定NZB和NZW品系对NZB X NZW(B/W)F1杂交小鼠循环中gp70 IC自发出现的遗传贡献,我们检测了雌性NZB、NZW、(NZB X NZW)F1(B/W F1)、B/W F1 X NZW回交小鼠以及B/W F1 X NZB回交小鼠中的这些免疫复合物。在B/W F1小鼠中发现的gp70 IC量最高,而在NZW小鼠中最低,平均血清水平的顺序为B/W F1、B/W F1 X NZB、B/W F1 X NZW、NZB和NZW。遗传分析表明,有两个主要的显性基因参与了这些gp70 IC的形成,一个来自NZB,另一个来自NZW。NZB品系的一个显性基因决定了这些免疫复合物的形成,其程度在很大程度上被NZW基因修饰(增强)。此外,对B/W F1 X NZW回交研究中获得的数据进行统计分析表明,还存在另一个显性NZB基因,它也与另一个NZB基因协同调节gp70 IC的形成程度。由于所有这些新西兰小鼠的游离gp70血清水平都很高,gp70 IC的形成代表了基因对抗gp70抗体产生的作用。连锁研究表明,NZB和NZW的两个主要基因都与H - 2复合体松散连锁,但与所检测的Mup - 1或毛色基因座均无连锁关系。在B/W F1 X NZW和B/W F1 X NZB回交小鼠中,蛋白尿的发生率与gp70 IC的血清水平密切相关。

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