IKK1-deficient mice exhibit abnormal development of skin and skeleton
IKK1-deficient mice exhibit abnormal development of skin and skeleton
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DOI：
10.1101/gad.13.10.1322
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发表时间：
1999-05-15
影响因子：
10.5
通讯作者：
Verma, IM
中科院分区：
文献类型：
--
作者：
Li, QT;Lu, QX;Verma, IM
I kappa B激酶(IKKS)IKK1和IKK2是参与核因子-kappa B激活的两个可能的I kappa Bα激酶。为了检测IKK1的体内功能，我培育了IKK1缺陷小鼠。突变的小鼠在围产期是致命的，并表现出广泛的发育缺陷。新生的突变小鼠皮肤有光泽、紧致和粘性，没有胡须。组织学分析显示表皮较厚，无法分化。四肢和尾巴包裹在皮肤内，不能正确地从躯干伸出。骨骼染色显示有继发性腭裂、胸骨裂开和门牙畸形。在IKK1基因缺陷的小鼠胚胎成纤维细胞(MEF)中，由肿瘤坏死因子α和IL-1介导的核因子-kappaB的激活被抑制。在没有IKK1的情况下，IKK复合体在体外能够磷酸化I kappa Bα和I kappa Bβ。我们的结果支持IKK1在核因子-kappa B激活中的作用，并揭示了它参与皮肤和骨骼的发育。我们进一步得出结论，两个相关的激酶IKK1和IKK2具有不同的功能，不能相互替代。
I kappa B kinases (IKKs) IKK1 and IKK2 are two putative I kappa B alpha kinases involved in NF-kappa B activation. To examine the in vivo functions of IKK1, me generated IKK1-deficient mice. The mutant mice are perinatally lethal and exhibit a wide range of developmental defects. Newborn mutant mice have shiny, taut, and sticky skin without whiskers. Histological analysis shows thicker epidermis, which is unable to differentiate. Limbs and tail are wrapped inside the skin and do not extend properly out of the body trunk. Skeleton staining reveals a cleft secondary palate, split sternebra 6, and deformed incisors. NF-kappa B activation mediated by TNF alpha and IL-1 is diminished in IKK1-deficient mouse embryonic fibroblast (MEF) cells. The IKK complex in the absence of IKK1 is capable of phosphorylating I kappa B alpha and I kappa B beta in vitro. Our results support a role for IKK1 in NF-kappa B activation and uncover its involvement in skin and skeleton development. We conclude further that the two related kinases IKK1 and IKK2 have distinct functions and can not be substituted for each other's functions.