Accelerated proliferation and abnormal differentiation of epidermal keratinocytes in endo-beta-galactosidase C transgenic mice.
Transgenic (TG) mice that have systemically expressed endo-beta-galactosidase C (EndoGalC) have rough and flaky skin. This skin phenotype is detectable around 5 days postnatal and becomes obscure by 2 weeks after birth. Their epidermis is thickened but the dermis and hair follicles are normal in structure. EndoGalC, which removes the terminal Galalpha1-3Gal disaccharide (alphaGal epitope), was expressed in the epidermis of TG mice. GS-IB4 lectin staining showed that the alphaGal epitope did not exist in the epidermis in TG but existed in wild-type (WT) mice. In TG mice, N-acetylglucosamines were exposed by EndoGalC, which is detected using GS-II lectin. To understand the cause of the epidermal thickening and skin phenotype, we examined the proliferation and differentiation of kerationocytes. BrdU-pulse-labeling revealed that proliferating keratinocytes increased approximately three-fold in TG epidermis compared to WT one. In TG epidermis, the expression domain of cytokeratin 14 increased from 1-2 layers to 4-5 layers and co-expressed with cytokeratin 6 and 10 in the upper layers. The layers expressing involucrin and loricrin also increased but those expressing filaggrin and transglutaminase looked normal. The localization of E-cadherin was similar in both TG and WT mice. Although TG mice showed delayed development of the barrier function around 8 days postnatal, they acquired the function by 12 days after birth. These results suggest that the absence of the alphaGal epitope or the exposed N-acetylglucosamine terminal could play a critical role in the proliferation of basal keratinocytes and differentiation of them into the spinous cells in newborn mice.
Misawa
Masako
M
Division of Resources Life Science, United Graduate School of Agricultural Sciences; Tottori University, 4-101 Koyama-Minami, Tottori 680-8553, Japan.
Watanabe
Satoshi
S
Ihara
Setsunosuke
S
Muramatsu
Takashi
T
Matsuzaki
Takashi
T
D000818:Animals; D002454:Cell Differentiation; D049109:Cell Proliferation; D000078404:Epidermal Cells; D018703:Founder Effect; D006026:Glycoside Hydrolases / Q000235:genetics* / Q000378:metabolism; D007150:Immunohistochemistry; D015603:Keratinocytes / Q000166:cytology* / Q000378:metabolism*; D051379:Mice; D008822:Mice, Transgenic; D012867:Skin / Q000378:metabolism
D006026:Glycoside Hydrolases; C057030:endo-beta-D-galactosidase C