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Titolo:
Expression of MK6a dominant-negative and C-terminal mutant transgenes in mice has distinct phenotypic consequences in the epidermis and hair follicle
Autore:
Wojcik, SM; Imakado, S; Seki, T; Longley, MA; Petherbridge, L; Bundman, DS; Bickenbach, JR; Rothnagel, JA; Roop, DR;
Indirizzi:
Baylor Coll Med, Dept Cell Biol, Houston, TX 77030 USA Baylor Coll Med Houston TX USA 77030 ept Cell Biol, Houston, TX 77030 USA Baylor Coll Med, Dept Dermatol, Houston, TX 77030 USA Baylor Coll Med Houston TX USA 77030 Dept Dermatol, Houston, TX 77030 USA Univ Queensland, Dept Biochem, Brisbane, Qld 4072, Australia Univ Queensland Brisbane Qld Australia 4072 Brisbane, Qld 4072, Australia Univ Iowa, Dept Anat & Cell Biol, Iowa City, IA 52242 USA Univ Iowa Iowa City IA USA 52242 nat & Cell Biol, Iowa City, IA 52242 USA
Titolo Testata:
DIFFERENTIATION
fascicolo: 2, volume: 65, anno: 1999,
pagine: 97 - 112
SICI:
0301-4681(199910)65:2<97:EOMDAC>2.0.ZU;2-H
Fonte:
ISI
Lingua:
ENG
Soggetto:
KERATIN INTERMEDIATE FILAMENTS; OUTER ROOT SHEATH; DIFFERENTIATION-SPECIFIC EXPRESSION; PACHYONYCHIA-CONGENITA TYPE-2; MOUSE SKIN CARCINOGENESIS; INNERMOST CELL LAYER; GROWTH-FACTOR-ALPHA; II KERATINS; EPIDERMOLYTIC HYPERKERATOSIS; STRATIFIED EPITHELIA;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
71
Recensione:
Indirizzi per estratti:
Indirizzo: Roop, DR Baylor Coll Med, Dept Cell Biol, 1 Baylor Plaza, Houston, TX 77030 USA Baylor Coll Med 1 Baylor Plaza Houston TX USA 77030 TX 77030 USA
Citazione:
S.M. Wojcik et al., "Expression of MK6a dominant-negative and C-terminal mutant transgenes in mice has distinct phenotypic consequences in the epidermis and hair follicle", DIFFERENTIA, 65(2), 1999, pp. 97-112

Abstract

Mouse keratin 6a (MK6a) is constitutively expressed in a single cell layerof the outer root sheath (ORS) of hair follicles, but its synthesis can beinduced in interfollicular epidermis including the basal cell layer in response to perturbing stimuli. A basally inducible human K6 (HK6) isoform hasnot been described, and it is not clear which of the known HK6 isoforms isexpressed in the ORS. In this study we show that expression of a dominant-negative MK6a construct (Delta 2B-P) in the interfollicular epidermis caused severe blistering and neonatal lethality, suggesting that mutations in a yet to be identified basally expressed HK6 isoform might result in a severeblistering phenotype. Surviving Delta 2B-P animals showed transgene expression only in isolated epidermal cells and not in all cells of the ORS, but nevertheless developed severe alopecia. Expression of two different C-terminal mutant transgenes also caused alopecia while a third C-terminal mutant had no phenotypic consequences. Electron microscopy revealed that Delta 2B-P expression resulted in the collapse of keratin filaments, while destruction of hair follicles in the two phenotypic C-terminal mutant lines occurredin the absence of filament abnormalities. The latter finding indicates that the innermost ORS cells are uniquely sensitive to expression of even slightly altered K6 proteins, suggesting that mutations affecting an HK6 isoform expressed in this cell layer could result in alopecia in humans as well.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 26/09/20 alle ore 14:12:37