NEMO/IKKγ-deficient mice model incontinentia pigmenti
NEMO/IKKγ-deficient mice model incontinentia pigmenti
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DOI：
10.1016/s1097-2765(00)80263-4
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发表时间：
2000-06-01
期刊：
影响因子：
16
通讯作者：
Pasparakis, M
中科院分区：
文献类型：
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作者：
Schmidt-Supprian, M;Bloch, W;Pasparakis, M
破坏编码NF-κ B必需调节因子（NEMO）的X连锁基因可导致雄性胚胎死亡，完全阻断促炎细胞因子对NF-κ B的激活，并干扰淋巴细胞的产生和/或持续存在。杂合子雌性小鼠出现斑片状皮肤病变，伴有大量粒细胞浸润和过度增殖，角质形成细胞凋亡增加。患病动物表现出严重的生长迟缓和早期死亡。存活的小鼠几乎完全恢复，大概是通过清除皮肤上NEMO缺陷的角质形成细胞。杂合子女性的配偶致死率和惊人相似的皮肤病变是人类遗传性疾病色素失禁症（IP）的标志。再加上最近发现人类NEMO基因突变导致IP，我们的结果表明我们已经为这种疾病建立了小鼠模型。
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. Mate 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.