Host modifier genes affect mouse autoimmunity induced by the lpr gene.
Host modifier genes affect mouse autoimmunity induced by the lpr gene.
复制标题
宿主修饰基因影响 lpr 基因诱导的小鼠自身免疫。
DOI：
--
复制
发表时间：
1997
影响因子：
6
通讯作者：
Hiroshi Hiai
中科院分区：
文献类型：
--
作者：
Yun Wang;Masato Nose;Toshiyuki Kamoto;M. Nishimura;Hiroshi Hiai
通过CD 95的凋亡信号传递的缺陷是lpr或gld小鼠中淋巴细胞增殖和自身免疫的重要遗传机制。然而，疾病表现在很大程度上受宿主遗传背景的影响。为了鉴定和定位这种修饰lpr基因效应的宿主基因，即lpr修饰物（Lprm）基因，对82只MRL/lpr x（MRL/lpr x C3 H/lpr）F1小鼠进行免疫病理学和遗传学分析。在不同的小鼠组中观察到回交小鼠中的高度血管炎和肾小球肾炎。微卫星分析显示，有两个宿主基因影响血管炎的发生，Lprm 1（染色体4）和Lprm 2（染色体3）。隐性MRL等位基因在Lprm 1增强血管炎发生在两种性别，而Lprm 2抑制其发展选择性的女性。这两个基因的基因型组合解释了MRL/lpr和C3 H/lpr小鼠杂交以及血管炎易感重组近交系McH 5/lpr中血管炎的严重程度。隐性MRL等位基因在Lprm 3（14号染色体）抑制肾小球肾炎。脾脏的重量增加了隐性MRL等位基因在Lprm 4（染色体5）产生的对数的比值分数为2.02的数量性状基因座分析。相反，腋窝淋巴结的重量增加了隐性MRL等位基因在2号染色体上的一个位点，但它的存在不支持的数量性状位点分析。抗dsDNA自身抗体的滴度由16号染色体上的基因座Lprm 5控制，其具有3.41的比值分数的对数。可能的候选基因Lprm基因推导出他们的地图位置进行了讨论，并与迄今报道的自身免疫基因进行比较。总之，lpr突变引起的自身免疫性疾病表现分别受到多个宿主基因的影响。
A defect in apoptotic signal transmission through CD95 is an essential genetic mechanism for lymphoproliferation and autoimmunities in lpr or gld mice. However, disease manifestations are largely affected by the host genetic background. To identify and map such host genes modifying lpr gene effect, ie, the lpr modifier (Lprm) genes, 82 MRL/lpr x (MRL/lpr x C3H/lpr) F1 mice were subjected to immunopathological and genetical analyses. High-grade vasculitis and glomerulonephritis among backcross mice were observed in separate groups of mice. Microsatellite analysis revealed that there were two host genes affecting the occurrence of vasculitis, Lprm1 (chromosome 4) and Lprm2 (chromosome 3). A recessive MRL allele at Lprm1 enhanced vasculitis to occur in both sexes, whereas that of Lprm2 inhibited its development selectively in females. Genotype combinations of these two genes explained the severity of vasculitis in crosses of MRL/lpr and C3H/lpr mice and also the vasculitis-prone recombinant inbred strain McH5/lpr. A recessive MRL allele at Lprm3 (chromosome 14) suppressed glomerulonephritis. The weight of the spleen was increased by a recessive MRL allele at Lprm4 (chromosome 5) yielding a logarithm of odds score of 2.02 in a quantitative trait locus analysis. In contrast, the weight of axillary lymph nodes was increased by a recessive MRL allele at a locus on chromosome 2, but its presence was not supported by the quantitative trait locus analysis. The titer of anti-dsDNA autoantibody was controlled by the locus Lprm5 on chromosome 16, which had an logarithm of odds score of 3.41. Possible candidate genes for Lprm genes deduced from their map locations are discussed and compared with the autoimmunity genes reported thus far. In conclusion, autoimmune disease manifestations by the lpr mutation are affected by multiple host genes separately.
登录
查看更多内容
影响因子：
32.4
作者：
MOREL, L;RUDOFSKY, UH;WAKELAND, EK
通讯作者：
WAKELAND, EK
DOI：
10.1172/jci118975
发表时间：
1996-10
期刊：
The Journal of clinical investigation
影响因子：
--
作者：
T. Vyse;C. G. Drake;S. Rozzo;E. Roper;S. Izui;B. Kotzin
通讯作者：
T. Vyse;C. G. Drake;S. Rozzo;E. Roper;S. Izui;B. Kotzin
异常的lpr双阴性T细胞在体内无法增殖。
DOI：
10.1006/clin.1995.1026
发表时间：
1995
期刊：
Clinical immunology and immunopathology
影响因子：
--
作者：
Sobel,ES;Kakkanaiah,VN;Rapoport,RG;Eisenberg,RA;Cohen,PL
通讯作者：
Cohen,PL
新西兰黑人对狼疮样肾病的贡献分析。
DOI：
--
发表时间：
1995
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Drake,CG;Rozzo,SJ;Hirschfeld,HF;Smarnworawong,NP;Palmer,E;Kotzin,BL
通讯作者：
Kotzin,BL
小鼠 SLE 血管病变分析。
DOI：
--
发表时间：
1983
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Berden,JH;Hang,L;McConahey,PJ;Dixon,FJ
通讯作者：
Dixon,FJ