Yu C C, Tsui H W, Ngan B Y, Shulman M J, Wu G E, Tsui F W
Department of Immunology, University of Toronto, Ontario, Canada.
J Exp Med. 1996 Feb 1;183(2):371-80. doi: 10.1084/jem.183.2.371.
Hematopoietic cell phosphatase (HCP), encoded by the hcph gene, (also called PTP1C, SHP, SH-PTP1, and PTPN6) is deficient in motheaten (me/me), and the allelic viable motheaten (me(v)/me(v)) mice. Since HCP is expressed in many cell types and protein phosphorylation is a major mechanism of regulating protein function, it is not surprising that the motheaten phenotype is pleiotropic. It is commonly thought that immune system involvement causes this disease. If so, the motheaten disease ought to be alleviated when the recombination activation gene-1 (RAG-1) is disrupted because there will be no V(D)J rearrangement and thus impaired development of B and T cells. We bred homozygous, double-mutant me(v)/me(v) x RAG 1 -/- mice and found that, in fact, inflamed paws, and splenomegaly with elevated myelopoiesis. Thus, except for autoantibodies, the motheaten phenotype does not depend on the presence of B and T cells. This observation cautions the use of motheaten mice as a model of autoimmune disease.
造血细胞磷酸酶（HCP）由hcph基因编码（也称为PTP1C、SHP、SH-PTP1和PTPN6），在“脱毛”（me/me）及等位基因存活的“脱毛”（me(v)/me(v)）小鼠中存在缺陷。由于HCP在多种细胞类型中表达，且蛋白质磷酸化是调节蛋白质功能的主要机制，因此“脱毛”小鼠的表型具有多效性也就不足为奇了。人们普遍认为免疫系统受累导致了这种疾病。如果是这样，当重组激活基因-1（RAG-1）被破坏时，“脱毛”病应该会得到缓解，因为不会发生V(D)J重排，从而B细胞和T细胞的发育受损。我们培育了纯合双突变的me(v)/me(v)×RAG 1 -/-小鼠，发现实际上爪子发炎，脾脏肿大且骨髓生成增加。因此，除自身抗体外，“脱毛”表型并不依赖于B细胞和T细胞的存在。这一观察结果提醒人们谨慎使用“脱毛”小鼠作为自身免疫性疾病的模型。
