Migeon B R, Brown T R, Axelman J, Migeon C J
Proc Natl Acad Sci U S A. 1981 Oct;78(10):6339-43. doi: 10.1073/pnas.78.10.6339.
We have established a cell line from mouse kidney cells expressing the tfm mutation and showed that these cells lack androgen binding activity. A subclone of these simian virus 40 (SV40)-transformed cells (6TGR-SV-tfm) selected in 6-thioguanine and lacking hypoxanthine phosphoribosyltransferase was used to produce a series of mouse--human hybrids containing the normal human X chromosome or various X autosome-translocation chromosomes (expressing only segments of the human X chromosome). When the androgen receptor locus (AR) was present in the hybrid, the number of receptor sites and kinetics of binding were similar to that in the human parental cells. Analysis of hybrids with partial human X chromosomes by using assays for X chromosome-linked enzymes and for the androgen receptor protein indicate that the AR locus on the human X chromosome is near the centromere between Xq13 and Xp11 and is proximal to the locus for phosphoglycerate kinase. Hybrids derived from 6TGR-SV-tfm mouse cells and human labial fibroblasts from an XY individual with the ar- form of androgen insensitivity have no binding activity. The lack of complementation indicates that the X chromosome-linked mutations in mouse and man affect homologous loci and supports the evolutionary conservation of X chromosomal loci in mammals; however, the position of the locus on the human X chromosome indicates that intrachromosomal rearrangement has occurred.
我们从表达tfm突变的小鼠肾细胞中建立了一个细胞系，并表明这些细胞缺乏雄激素结合活性。在6-硫鸟嘌呤中筛选出的、缺乏次黄嘌呤磷酸核糖基转移酶的这些猴病毒40（SV40）转化细胞（6TGR-SV-tfm）的一个亚克隆，被用于产生一系列含有正常人类X染色体或各种X-常染色体易位染色体（仅表达人类X染色体片段）的小鼠-人类杂种细胞。当杂种细胞中存在雄激素受体基因座（AR）时，受体位点的数量和结合动力学与人类亲代细胞相似。通过使用针对X染色体连锁酶和雄激素受体蛋白的检测方法对具有部分人类X染色体的杂种细胞进行分析表明，人类X染色体上的AR基因座靠近Xq13和Xp11之间的着丝粒，并且位于磷酸甘油酸激酶基因座的近端。来自6TGR-SV-tfm小鼠细胞和一名具有雄激素不敏感ar-形式的XY个体的人类唇成纤维细胞的杂种细胞没有结合活性。缺乏互补作用表明小鼠和人类中与X染色体连锁的突变影响同源基因座，并支持哺乳动物中X染色体基因座的进化保守性；然而，该基因座在人类X染色体上的位置表明发生了染色体内重排。
