Expression of MK6a dominant-negative and C-terminal mutant transgenes in mice has distinct phenotypic consequences in the epidermis and hair follicle.

摘要: Mouse keratin 6a (MK6a) is constitutively expressed in a single cell layer of the outer root sheath (ORS) hair follicles, but its synthesis can be induced interfollicular epidermis including basal response to perturbing stimuli. A basally inducible human K6 (HK6) isoform has not been described, and it clear which known HK6 isoforms ORS. In this study we show that expression dominant-negative MK6a construct (Δ2B-P) caused severe blistering neonatal lethality, suggesting mutations yet identified might result phenotype. Surviving Δ2B-P animals showed transgene only isolated epidermal cells all ORS, nevertheless developed alopecia. Expression two different C-terminal mutant transgenes also alopecia while third had no phenotypic conse- quences. Electron microscopy revealed resulted collapse filaments, destruction follicles lines occurred absence filament abnormalities. The latter finding indicates innermost ORS are uniquely sensitive even slightly altered proteins, affecting an could humans as well.