A NONSENSE MUTATION OF THE HUMAN LUTEINIZING-HORMONE RECEPTOR GENE IN LEYDIG-CELL HYPOPLASIA
A NONSENSE MUTATION OF THE HUMAN LUTEINIZING-HORMONE RECEPTOR GENE IN LEYDIG-CELL HYPOPLASIA
复制标题
DOI：
10.1093/hmg/4.8.1429
复制
发表时间：
1995-08-01
影响因子：
3.5
通讯作者：
CHAN, WY
中科院分区：
文献类型：
--
作者：
LAUE, L;WU, SM;CHAN, WY
间质细胞发育不全（Leydig cell hypoplasia，LCH）是男性假两性畸形的一种表现形式，表现为间质细胞分化和睾酮分泌功能受损。本文报道了首例LCH姐妹篇的人促黄体生成激素受体（human luteinizing hormone receptor，hLHR）基因第11外显子无义突变（A1635 C）。该突变通过在hLHR的跨膜螺旋5中的残基545处引入终止密码子而导致受体功能丧失。与野生型hLHR相比，在稳定转染编码hLHR-t545的cDNA的人胚肾细胞中，截短的hLHR（hLHR-t545）的表面表达减少，并且hCG诱导的cAMP积累受损。这些结果证实，hLHR基因外显子11中的单碱基突变可以产生hLMR的失活以及激活。此外，他们证明了跨膜螺旋5和hLHR的C-末端胞质尾区之间的功能结构域是受体的正常细胞表面表达和信号转导所需的。
Leydig cell hypoplasia (LCH) is a form of male pseudohermaphroditism in which Leydig cell differentiation and testosterone production are impaired, This report describes the first case of a nonsense mutation (A1635C) in exon 11 of the human luteinizing hormone receptor (hLHR) gene in two sisters with LCH. This mutation causes loss of function of the receptor by introducing a stop codon at residue 545 in transmembrane helix 5 of the hLHR. Surface expression of the truncated hLHR (hLHR-t545) in human embryonic kidney cells stably transfected with cDNA encoding hLHR-t545 was diminished compared to the wild-type hLHR and hCG-induced cAMP accumulation was impaired, These results establish that single base mutations in exon 11 of the hLHR gene can produce inactivation as well as activation of the hLMR. Furthermore, they demonstrate that functional domains between transmembrane helix 5 and the C-terminal cytoplasmic tail of the hLHR are required for normal cell surface expression of the receptor and signal transduction.