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


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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Figure 1: Genotypic and phenotypic analysis of mice deficient for Irf6.
Figure 2: Skeletal defects in mice deficient for Irf6.
Figure 3: Histologic and molecular analyses of Irf6-null E17.5 embryos.
Figure 4: Epidermal adhesions and desmosomal structure in Irf6-null embryos.
Figure 5: Expression of stratifin and Ikka in skin from Irf6-null E17.5 embryos.

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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.).

Author information




This study was designed by B.C.S., S.K., J.C.M. and B.Y.; phenotype assessment was performed by C.R.I., A.K., K.J.T., M.D. and S.L.G.; genotype assessment was performed by M.I.M. and A.K.; data analysis was performed by S.S. and M.L.; and C.R.I., B.C.S., J.C.M., M.L., A.K. and M.D. contributed to the writing of the paper.

Corresponding author

Correspondence to Brian C Schutte.

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The authors declare no competing financial interests.

Supplementary information

Supplementary Table 1

Change in gene expression for epidermal differentiation markers in Irf6 wild-type versus null skin. (PDF 55 kb)

Supplementary Table 2

Sequence of PCR primers for genotyping Irf6 gene trap allele. (PDF 38 kb)

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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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