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

Nat Genet. 2006 Nov;38(11):1335-40. doi: 10.1038/ng1903. Epub 2006 Oct 15.


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. Mice deficient for Irf6 have not been reported, but in humans, mutations in IRF6 cause two mendelian orofacial clefting syndromes, and genetic variation in IRF6 confers risk for isolated cleft lip and palate. 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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Cell Differentiation
  • Cell Proliferation
  • Craniofacial Abnormalities / genetics*
  • Extremities / embryology
  • Female
  • Gene Expression Profiling
  • Gene Expression Regulation, Developmental
  • Head / embryology
  • Interferon Regulatory Factors / genetics*
  • Keratinocytes / cytology
  • Keratinocytes / metabolism
  • Limb Deformities, Congenital / genetics*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Morphogenesis / genetics*
  • Pregnancy
  • Skin / embryology
  • Skin Abnormalities / genetics*


  • IRF6 protein, human
  • Interferon Regulatory Factors

Associated data

  • GEO/GSE5800