Relation of skin polyamines to the hairless phenotype in transgenic mice overexpressing spermidine/spermine N-acetyltransferase.
We recently generated a transgenic mouse line with activated polyamine catabolism due to overexpression of spermidine/spermine N1-acetyltransferase. Phenotypic changes in these animals included permanent loss of hair at the age of 3 wk. We have now further explored development of hair loss during early postnatal life. The first hair cycle appeared to be completed normally in the transgenic animals. At postnatal day 15, although macroscopically indistinguishable from their syngenic littermates, the transgenic animals already showed microscopically signs of hair follicle degeneration. Wild-type mice started their second anagen phase at day 27, whereas the transgenic animals did not display functional hair follicles at that time. Hair follicles were replaced by dermal cysts and epidermal utriculi. Analysis of skin polyamines revealed that the transgenic animals continuously overaccumulated putrescine. The view that an overaccumulation of putrescine was related to the disturbed hair follicle development was strengthened by the finding that doubly transgenic mice overexpressing, both spermidine/spermine N1-acetyltransferase and ornithine decarboxylase and with extremely high levels of putrescine in the skin, showed distinctly more severe skin changes compared with the singly transgenic animals. Interest ingly, in spite of their hairless phenotype, the spermidine/spermine N1-acetyltransferase transgenic mice, were significantly more resistant to the development of papillomas in response to the two-stage skin carcinogenesis. Analysis of skin polyamines indicated that the syngenic mice tripled their spermidine content when exposed to promotion, whereas the transgenic animals showed only modest changes. These results suggest that putrescine plays a pivotal part in normal hair follicle development.
Pietilä
M
M
A.I. Virtanen Institute for Molecular Sciences, University of Kuopio, Kuopio, Finland.
Parkkinen
J J
JJ
Alhonen
L
L
Jänne
J
J
D015127:9,10-Dimethyl-1,2-benzanthracene; D000123:Acetyltransferases / Q000235:genetics / Q000378:metabolism*; D000375:Aging / Q000502:physiology; D000505:Alopecia / Q000235:genetics*; D000818:Animals; D000831:Animals, Newborn / Q000254:growth & development / Q000502:physiology; D002273:Carcinogens; D051379:Mice; D008822:Mice, Transgenic / Q000235:genetics; D009367:Neoplasm Staging; D009955:Ornithine Decarboxylase / Q000378:metabolism; D010212:Papilloma / Q000139:chemically induced / Q000473:pathology; D010641:Phenotype; D011073:Polyamines / Q000378:metabolism*; D011700:Putrescine / Q000378:metabolism; D012016:Reference Values; D012867:Skin / Q000378:metabolism* / Q000473:pathology; D012878:Skin Neoplasms / Q000139:chemically induced / Q000473:pathology; D013095:Spermidine / Q000378:metabolism* / Q000502:physiology; D013755:Tetradecanoylphorbol Acetate; D013997:Time Factors; D000099228:Diamine N-Acetyltransferase
D015127:9,10-Dimethyl-1,2-benzanthracene; D000123:Acetyltransferases; D002273:Carcinogens; D009955:Ornithine Decarboxylase; D011073:Polyamines; D011700:Putrescine; D013095:Spermidine; D013755:Tetradecanoylphorbol Acetate; D000099228:Diamine N-Acetyltransferase