Exons 5–15 of Kazrin Are Dispensable for Murine Epidermal Morphogenesis and Homeostasis

11 páginas, 6 figuras.Kazrin binds to periplakin and ARVCF catenin, and regulates adhesion and differentiation of cultured human keratinocytes. To explore kazrin function in vivo, we generated a kazrin gene-trap mouse in which only exons 1–4 were expressed, fused to b-galactosidase. On transient transfection, the protein encoded by exons 1–4 did not enter the nucleus, but did cause keratinocyte shape changes. The mice had no obvious defects in skin development or homeostasis, and periplakin and desmoplakin localization was normal. Expression of the kazrin-b-galactosidase fusion protein faithfully reported endogenous kazrin expression. Kazrin was not expressed in embryonic epidermis and was first detected at postnatal day 1. In adult mice, epidermal kazrin expression was less widespread than in humans and Xenopus, being confined to the bulb of anagen hair follicles, the infundibulum, and parakeratotic tail epidermis. In anagen bulbs, kazrin was expressed by a band of cells with elongated morphology and low desmoplakin levels, suggesting a role in morphogenetic cell movements. We conclude that exons 5–15 of kazrin, encoding the nuclear localization signal and C-terminal domain, are not required for epidermal development and function. The previously reported role of kazrin in regulating cell shape appears to reside within the N-terminal coiled-coil domain encoded by exons 1–4.This work was supported by Cancer Research UK, the Medical Research Council, the Wellcome Trust, and EU FP7. We gratefully acknowledge the support of Cambridge University and Hutchison Whampoa. Individual authors were supported by the following fellowships: Herchel Smith (MC), FEBS (SC), and the NIH (LS).Peer reviewe