In this strain a gene construct (VICTR48), containing a neomycin resistance (neo), integrated downstream of the splice donor site of the interferon regulatory factor 6 (Irf6) gene. Mice that are heterozygous for the gene trap mutation are viable and fertile. Homozygotes have a perinatal lethal phenotype. IRF6 is a transcription factor involved in keratinocyte, epidermal, and epithelial cell proliferation as well as craniofacial development. IRF6 is expressed in the skin and oral epithelium from E17.5. Heterozygous embryos have oral adhesions between epithelial layers of the maxilla and mandible that are incompletely penetrant. These oral adhesions are transient, as they are more common at E13.5 than E17.5, and do not impede subsequent orofacial development in the C57BL/6 background.
Homozygous embryos have taut, shiny skin, lack external ears and have snouts and jaws shorter and more rounded than their wild-type littermates. They also have short forelimbs that lacked visible digits, a single caudal projection that lacked visible hindlimbs and tail, and a cleft secondary palate. Their skeleton also exhibits a split xiphoid process, shortened sternum, delayed ossification of sternum and vertebrae, and synostosis. These mice may be useful for studying craniofacial development and keratinocytes differentiation.
