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.
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The authors wish to acknowledge technical assistance from E. Sweezer, R. Cao, T. Kinney, S. Bullard, H. Mishima and A. Lidral. We also thank K. Walters and J. Shao of the Central Microscopy Research Facility and K. Knudtson of the DNA Core Facility at the University of Iowa. We wish to thank R. Richardson and M. Dixon for sharing results before publication. This work was supported in part by US National Institutes of Health grants DE16215 (J.C.M., B.C.S., M.L., B.Y.), DE13513 (B.C.S.) and DE08559 (J.C.M.).
The authors declare no competing financial interests.
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Ingraham, C., Kinoshita, A., Kondo, S. et al. Abnormal skin, limb and craniofacial morphogenesis in mice deficient for interferon regulatory factor 6 (Irf6). Nat Genet 38, 1335–1340 (2006). https://doi.org/10.1038/ng1903
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