Vogeli G, Wood L, McNab A R, Kaytes P, Wagner T E, Rea T J, Groppi V, Waldon D J, Kawabe T T, Buhl A E
Upjohn Company, Kalamazoo, Michigan 49001.
Ann N Y Acad Sci. 1991 Dec 26;642:21-30; discussion 30-1. doi: 10.1111/j.1749-6632.1991.tb24377.x.
We analyzed the effect of minoxidil on hair follicles isolated from transgenic mice. These transgenic animals synthesize the reporter enzyme CAT in their hair follicles only during the active phases of hair growth. The recombinant gene used to generate these mice contained the bacterial enzyme CAT under the control of the promoter from the gene of UHS protein. Studies using in situ hybridization showed that UHS proteins are expressed specifically in the matrix cells of the hair follicle during the terminal stages of hair differentiation. Hence the expression of the UHS proteins is a clear sign of active hair growth. With other in situ hybridization studies we demonstrated that CAT mRNA is expressed in differentiating matrix cells of the hair shaft in a location similar to that in which mRNA encodes UHS proteins. Thus we can use the levels of CAT activity as a measure of hair growth. We have confirmed that expression of the transgene is found in hair that is high in anagen and low in catagen follicles. The usefulness of our model was further demonstrated by showing that minoxidil, a drug that stimulates hair growth, increased the expression of CAT in cultured hair follicles. Thus we have demonstrated that expression of this reporter gene is sensitive, hair specific, and also useful for monitoring effects in cultured hair follicles. Hence these transgenic mice provide a model system for studying the biology of hair growth.
我们分析了米诺地尔对从转基因小鼠分离出的毛囊的影响。这些转基因动物仅在毛发生长的活跃期在其毛囊中合成报告酶氯霉素乙酰转移酶（CAT）。用于培育这些小鼠的重组基因包含在UHS蛋白基因启动子控制下的细菌酶CAT。使用原位杂交的研究表明，在毛发分化的终末阶段，UHS蛋白在毛囊的基质细胞中特异性表达。因此，UHS蛋白的表达是毛发生长活跃的明显标志。通过其他原位杂交研究，我们证明CAT mRNA在毛干分化的基质细胞中表达，其位置与编码UHS蛋白的mRNA的位置相似。因此，我们可以将CAT活性水平用作毛发生长的指标。我们已证实，在生长期毛囊含量高而退行期毛囊含量低的毛发中可发现转基因的表达。通过表明刺激毛发生长的药物米诺地尔可增加培养毛囊中CAT的表达，进一步证明了我们模型的实用性。因此，我们已证明该报告基因的表达具有敏感性、毛发特异性，并且对于监测培养毛囊中的效应也很有用。因此，这些转基因小鼠为研究毛发生长生物学提供了一个模型系统。
