A single nucleotide substitution introduces a premature termination codon into the androgen receptor gene of a patient with receptor-negative androgen resistance.
A single nucleotide substitution introduces a premature termination codon into the androgen receptor gene of a patient with receptor-negative androgen resistance.
复制标题
单核苷酸取代将提前终止密码子引入受体阴性雄激素抵抗患者的雄激素受体基因中。
DOI：
10.1172/jci114599
复制
发表时间：
1990
期刊：
影响因子：
--
通讯作者：
McPhaul,MJ
中科院分区：
文献类型：
--
作者：
Marcelli,M;Tilley,WD;Wilson,CM;Wilson,JD;Griffin,JE;McPhaul,MJ
雄激素受体的突变损害了5 -二氢睾酮和睾酮的作用，导致男性性发育异常。雄激素受体基因组织的定义允许我们检查9例雄激素抗性患者的结构，这些患者在培养成纤维细胞中表现出缺乏5 -二氢睾酮结合（受体阴性雄激素抗性）。使用针对每个编码外显子的标记探针，我们在这些患者中没有发现雄激素受体基因的重排、插入或缺失。为了分析这些受体阴性患者的遗传缺陷，我们使用聚合酶链反应扩增了9名患者的雄激素受体基因的每个外显子。在所有患者中，每个扩增的外显子片段的大小与正常个体相同。在这些患者中，确定了雄激素受体整个编码区的核苷酸序列。在794号氨基酸外显子6处发现了一个过早终止密码子的单核苷酸替换。S1核酸酶保护试验表明，在该患者的皮肤成纤维细胞中存在正常水平的雄激素受体mRNA。将含有794位终止密码子的突变雄激素受体cDNA转染真核细胞，免疫印迹结果显示，形成正常数量的受体蛋白，但表达的蛋白不结合5 α -二氢睾酮。这些发现表明，在雄激素受体794氨基酸上存在一个过早终止密码子是该患者雄激素耐药的原因。图片
Mutations of the androgen receptor that impair the action of 5 alpha-dihydrotestosterone and testosterone result in abnormal male sexual development. The definition of the organization of the androgen receptor gene has permitted us to examine its structure in nine patients with androgen resistance that exhibit absent 5 alpha-dihydrotestosterone binding in cultured fibroblasts (receptor-negative androgen resistance). Using labeled probes specific for each individual coding exon, we find no gross rearrangements, insertions, or deletions of the androgen receptor gene in these patients. To analyze the genetic defect in these receptor-negative patients, we used the polymerase chain reaction to amplify each individual exon of the androgen receptor gene in nine affected patients. In all patients, the size of each amplified exon segment was identical to that in normal individuals. The nucleotide sequence of the entire coding region of the androgen receptor was determined in one of these patients. A single nucleotide substitution was identified that results in a premature termination codon in exon 6 at amino acid 794. S1 nuclease protection assays demonstrated that normal levels of androgen receptor mRNA are present in skin fibroblasts of this patient. Transfection of a mutated androgen receptor cDNA containing a termination codon at position 794 into eukaryotic cells resulted in formation of a normal amount of receptor protein, as indicated by immunoblotting, but the expressed protein does not bind 5 alpha-dihydrotestosterone. These findings suggest that the presence of a premature termination codon at amino acid 794 of the androgen receptor is the cause of androgen resistance in this patient.Images
登录
查看更多内容
影响因子：
64.5
作者：
GREEN, N;ALEXANDER, H;LERNER, RA
通讯作者：
LERNER, RA
使用从噬菌体 M13mp 模板合成的单链 [32P]DNA 探针进行高灵敏度 S1 作图。
影响因子：
3.5
作者：
J. Burke
通讯作者：
J. Burke
人类不完全形式雄激素抵抗的发病机制的研究。
DOI：
10.1210/jcem-45-6-1137
发表时间：
1977
期刊：
The Journal of clinical endocrinology and metabolism
影响因子：
--
作者：
J. Griffin;Jean D. Wilson
通讯作者：
Jean D. Wilson
影响因子：
56.9
作者：
EVANS, RM
通讯作者：
EVANS, RM
影响因子：
--
作者：
LUBAHN, DB;JOSEPH, DR;WILSON, EM
通讯作者：
WILSON, EM