Epidermal hyperproliferation and decreased skin barrier function in mice overexpressing stratum corneum chymotryptic enzyme.
Stratum corneum chymotryptic enzyme (SCCE; also known as kallikrein 7) is a serine protease that may have an important role in the skin desquamation process. We have recently described transgenic mice overexpressing human SCCE in suprabasal epidermal keratinocytes, leading to increased epidermal thickness, hyperkeratosis, dermal inflammation and signs of severe pruritus in older animals. In order to further evaluate the scce-transgenic mice as a potential disease model, we compared transgenic animals and wild-type littermates for patterns of epidermal keratin expression, in situ hybridization of scce-mRNA, scratching behaviour and measurements of transepidermal water loss (TEWL). In 3-day-old mice, despite readily detectable amounts of human scce-mRNA in the epidermis of transgenic animals, there were no histological differences in skin appearance, and no differences could be found in epidermal expression of the keratins 5, 6 and 10. In mice 7-8 weeks of age and older, there was strong suprabasal expression of keratins 5 and 6 in the epidermis of transgenic animals, suggesting that the thickened epidermis in these animals is the result of keratinocyte hyperproliferation. In transgenic animals 11 weeks of age and older there was an increased frequency of scratching, suggestive of pruritus, and also signs of a deteriorating skin barrier function, as reflected by an increased TEWL. There was no correlation between increased TEWL and increased frequency of scratching in individual animals, suggesting that the defect barrier function was not an effect of skin damage caused by scratching.
Ny
Annelii
A
Department of Public Health and Clinical Medicine and Department of Dermatology and Venereology, Umeå University, Umeå, Sweden.
Egelrud
Torbjörn
T
D000818:Animals; D001834:Body Water / Q000378:metabolism; D004817:Epidermis / Q000378:metabolism / Q000473:pathology*; D017403:In Situ Hybridization; D007610:Kallikreins; D015603:Keratinocytes / Q000201:enzymology / Q000473:pathology; D007633:Keratins / Q000096:biosynthesis; D051379:Mice; D008822:Mice, Transgenic; D011537:Pruritus / Q000201:enzymology; D012697:Serine Endopeptidases / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D012879:Skin Physiological Phenomena
D007633:Keratins; C082472:KLK7 protein, human; D007610:Kallikreins; D012697:Serine Endopeptidases