Schmidt-Supprian M, Bloch W, Courtois G, Addicks K, Israël A, Rajewsky K, Pasparakis M
Institute for Genetics, University of Cologne, Federal Republic of Germany.
Mol Cell. 2000 Jun;5(6):981-92. doi: 10.1016/s1097-2765(00)80263-4.
Disruption of the X-linked gene encoding NF-kappa B essential modulator (NEMO) produces male embryonic lethality, completely blocks NF-kappa B activation by proinflammatory cytokines, and interferes with the generation and/or persistence of lymphocytes. Heterozygous female mice develop patchy skin lesions with massive granulocyte infiltration and hyperproliferation and increased apoptosis of keratinocytes. Diseased animals present severe growth retardation and early mortality. Surviving mice recover almost completely, presumably through clearing the skin of NEMO-deficient keratinocytes. Male lethality and strikingly similar skin lesions in heterozygous females are hallmarks of the human genetic disorder incontinentia pigmenti (IP). Together with the recent discovery that mutations in the human NEMO gene cause IP, our results indicate that we have created a mouse model for that disease.
编码核因子κB必需调节因子（NEMO）的X连锁基因的破坏会导致雄性胚胎致死，完全阻断促炎细胞因子对核因子κB的激活，并干扰淋巴细胞的产生和/或持续存在。杂合子雌性小鼠会出现片状皮肤病变，伴有大量粒细胞浸润以及角质形成细胞的过度增殖和凋亡增加。患病动物表现出严重的生长发育迟缓以及早期死亡。存活的小鼠几乎完全康复，推测是通过清除缺乏NEMO的角质形成细胞实现的。雄性致死以及杂合子雌性小鼠中惊人相似的皮肤病变是人类遗传性疾病色素失禁症（IP）的特征。连同最近发现人类NEMO基因突变会导致色素失禁症，我们的结果表明我们已经创建了该疾病的小鼠模型。
