Gene targeting of envoplakin, a cytoskeletal linker protein and precursor of the epidermal cornified envelope

Envoplakin, a member of the plakin family of cytoskeletal linker proteins, is localized in desmosomes of stratified epithelial cells and is a componen t of the epidermal cornified envelope. Gene targeting in mouse embryonic st em cells was used to generate a null allele of envoplakin. No envoplakin tr anscripts from the targeted allele could be detected in the skin of newborn mice. Mice homozygous for the targeted allele were born in the normal Mend elian ratio and were fertile. They did not develop any discernible patholog ical phenotype up to the age of I year. The ultrastructural appearance of c ornified envelopes from adult epidermis was indistinguishable between wild- type and knockout mice, and there was no evidence that the absence of envop lakin affected the subcellular distribution of periplakin or desmoplakin, t wo other plakins found in desmosomes. The proportion of immature cornified envelopes in the epidermis of newborn mice was greater in envoplakin-null a nimals than in heterozygous littermates or wild-type mice, and the envelope s had a larger surface area. This correlated with a slight delay in barrier acquisition during embryonic development. We conclude that although envopl akin is part of the scaffolding on which the cornified envelope is assemble d, it is not essential for envelope formation or epidermal barrier function .