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Abnormal skin, limb and craniofacial morphogenesis in mice deficient for interferon regulatory factor 6 (Irf6)

2006; Nature Portfolio; Volume: 38; Issue: 11 Linguagem: Inglês

10.1038/ng1903

1546-1718

Christopher R. Ingraham, Akira Kinoshita, Shinji Kondo, Baoli Yang, Samin A. Sajan, Kurt J Trout, Margaret Malik, Martine Dunnwald, Stephen L Goudy, Michael Lovett, Jeffrey C. Murray, Brian C. Schutte,

Craniofacial Disorders and Treatments

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 abnormalities1,2,3,4,5,6,7. Mice deficient for Irf6 have not been reported, but in humans, mutations in IRF6 cause two mendelian orofacial clefting syndromes8,9,10, and genetic variation in IRF6 confers risk for isolated cleft lip and palate11,12,13,14,15. 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.