Loci predisposing to autoimmunity in MRL-Fas lpr and C57BL/6-Faslpr mice.
Loci predisposing to autoimmunity in MRL-Fas lpr and C57BL/6-Faslpr mice.
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MRL-Fas lpr 和 C57BL/6-Faslpr 小鼠中易产生自身免疫的位点。
DOI：
10.1172/jci1817
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发表时间：
1998
期刊：
影响因子：
--
通讯作者：
Theofilopoulos,AN
中科院分区：
文献类型：
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作者：
Vidal,S;Kono,DH;Theofilopoulos,AN
背景基因决定了淋巴细胞蓄积的发生率和严重程度，以及系统性自身免疫的组织病理学表现，这些都是Fas lpr突变纯合子小鼠的特征。通过对274只MRL-Faslpr（重度疾病）和C57 BL/6-Faslpr（轻微疾病）杂交的F2小鼠进行区间作图，在（MRL-Faslpr x B6-Faslpr）F2 cross 1 -4（Lmb 1 -4）中，分别在第4、5、7和10号染色体上鉴定出与淋巴结病和/或脾肿大显著连锁的4个位点，命名为狼疮。Lmb 1、-2和3也与抗dsDNA抗体的产生有关，但与肾小球肾炎无关，而Lmb 4与肾小球肾炎有关。Lmb 2、Lmb 3和Lmb 4从MRL背景遗传，但有趣的是，Lmb 1来自C57 BL 16-Faslpr。然而，每个位点，无论菌株的起源，似乎是在一个加性的方式，虽然某些组合更有效。只有1号染色体上的一个单一的暗示位点可能与关节炎相关。在Faslpr菌株中鉴定与疾病表现具有高度显著连锁的基因座将使得有可能定位和克隆有助于自身免疫的新的遗传缺陷。
Background genes determine the incidence and severity of lymphoaccumulation and histopathologic manifestations of systemic autoimmunity in mice homozygous for the apoptosis-defective Faslpr mutation. By interval mapping of 274 F2 mice intercrossed between MRL-Faslpr (severe disease) and C57BL/6-Faslpr (minimal disease), four loci were identified with significant linkage to lymphadenopathy and/ or splenomegaly on chromosomes 4, 5, 7, and 10, which were named lupus in (MRL-Faslpr x B6-Faslpr)F2 cross1-4 (Lmb1-4), respectively. Lmb1, -2, and -3 were also linked to the production of anti-dsDNA antibodies, but not glomerulonephritis, whereas Lmb4 was associated with glomerulonephritis. Lmb2, -3, and -4 were inherited from the MRL background, but interestingly, Lmb1 was derived from the C57BL16-Faslpr. Nevertheless, each locus, regardless of the strain of origin, appeared to act in an additive manner, although certain combinations were more effective. Only a single suggestive locus on chromosome 1 could be correlated with arthritis. The identification of loci with highly significant linkage to disease manifestations in Faslpr strains will make it possible to map and clone new genetic defects contributing to autoimmunity.