Pietilä M, Parkkinen J J, Alhonen L, Jänne J
A.I. Virtanen Institute for Molecular Sciences, University of Kuopio, Kuopio, Finland.
J Invest Dermatol. 2001 May;116(5):801-5. doi: 10.1046/j.1523-1747.2001.01330.x.
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.
我们最近通过过表达亚精胺/精胺N1 - 乙酰转移酶生成了一种具有激活的多胺分解代谢的转基因小鼠品系。这些动物的表型变化包括在3周龄时永久性脱毛。我们现在进一步探究了出生后早期脱发的发展情况。转基因动物的第一个毛发周期似乎正常完成。在出生后第15天，尽管转基因动物在宏观上与同基因的同窝仔无明显差异，但在显微镜下已显示出毛囊退化的迹象。野生型小鼠在第27天开始其第二个生长期，而此时转基因动物没有功能性毛囊。毛囊被真皮囊肿和表皮小囊所取代。对皮肤多胺的分析表明，转基因动物持续过度积累腐胺。过表达亚精胺/精胺N1 - 乙酰转移酶和鸟氨酸脱羧酶且皮肤中腐胺水平极高的双转基因小鼠与单转基因动物相比，皮肤变化明显更严重，这一发现强化了腐胺过度积累与毛囊发育紊乱有关的观点。有趣的是，尽管亚精胺/精胺N1 - 乙酰转移酶转基因小鼠表现出无毛表型，但在两阶段皮肤致癌过程中，它们对乳头瘤的发生具有显著更高的抵抗力。对皮肤多胺的分析表明，同基因小鼠在受到促癌作用时其亚精胺含量增加了两倍，而转基因动物仅表现出适度变化。这些结果表明腐胺在正常毛囊发育中起关键作用。
