Abnormal skin, limb and craniofacial morphogenesis in mice deficient for interferon regulatory factor 6 (Irf6)
Abnormal skin, limb and craniofacial morphogenesis in mice deficient for interferon regulatory factor 6 (Irf6)
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DOI：
10.1038/ng1903
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发表时间：
2006-11-01
期刊：
影响因子：
30.8
通讯作者：
Schutte, Brian C.
中科院分区：
文献类型：
--
作者：
Ingraham, Christopher R.;Kinoshita, Akira;Schutte, Brian C.
转录因子类似物可能在特定组织中的分期或重叠表达中共享共同的作用，如在HOX家族中。在其他情况下，家族成员在一系列胚胎、分化或反应途径中扮演着不同的角色(如在Tbx和Pax家族中)。对于干扰素调节因子(IRF)转录因子家族，IRF1、IRF2、IRF3、IRF4、IRF5、IRF7、IRF8或IRF9缺陷小鼠的免疫反应存在缺陷，但没有表现出胚胎异常(1-7)。IRF6缺失的小鼠还没有报道，但在人类中，IRF6的突变会导致两种孟德尔口面部裂开综合征(8-10)，而IRF6的基因变异会增加孤立的唇腭裂的风险(11-15)。在此，我们报告了IRF6基因缺陷的小鼠皮肤、四肢和颅面发育异常。组织学和基因表达分析表明，主要缺陷是角质形成细胞的分化和增殖。这项研究描述了IRF家族成员在表皮发育中的新角色。
Transcription factor paralogs may share a common role in staged or overlapping expression in specific tissues, as in the Hox family. In other cases, family members have distinct roles in a range of embryologic, differentiation or response pathways (as in the Tbx and Pax families). For the interferon regulatory factor (IRF) family of transcription factors, mice deficient in Irf1, Irf2, Irf3, Irf4, Irf5, Irf7, Irf8 or Irf9 have defects in the immune response but show no embryologic abnormalities(1-7). Mice deficient for Irf6 have not been reported, but in humans, mutations in IRF6 cause two mendelian orofacial clefting syndromes(8-10), and genetic variation in IRF6 confers risk for isolated cleft lip and palate(11-15). Here we report that mice deficient for Irf6 have abnormal skin, limb and craniofacial development. Histological and gene expression analyses indicate that the primary defect is in keratinocyte differentiation and proliferation. This study describes a new role for an IRF family member in epidermal development.