Evidence that the diabetes gene encodes the leptin receptor: Identification of a mutation in the leptin receptor gene in db/db mice
Evidence that the diabetes gene encodes the leptin receptor: Identification of a mutation in the leptin receptor gene in db/db mice
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DOI：
10.1016/s0092-8674(00)81294-5
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发表时间：
1996-02-09
期刊：
影响因子：
64.5
通讯作者：
Morgenstern, JP
中科院分区：
文献类型：
--
作者：
Chen, H;Charlat, O;Morgenstern, JP
OB-R是瘦素的高亲和力受体，瘦素是调节体重的重要循环信号。我们鉴定了编码具有长胞内结构域的小鼠OB-R形式的可变剪接转录物，db/db小鼠也产生这种可变剪接转录物，但是具有提前终止胞内结构域的106 nt插入。我们进一步鉴定了db/db小鼠基因组OB-R序列中的G->T点突变。该突变产生供体剪接位点，其将106 nt区域转化为OB-R转录物中保留的新外显子。我们预测OB-R的长胞内结构域形式对于启动胞内信号转导是至关重要的，并且作为推论，不能产生这种形式的OB-R导致在db/db小鼠中发现的严重肥胖表型。
OB-R is a high affinity receptor for leptin, an important circulating signal for the regulation of body weight. We identified an alternatively spliced transcript that encodes a form of mouse OB-R with a long intracellular domain, db/db mice also produce this alternatively spliced transcript, but with a 106 nt insertion that prematurely terminates the intracellular domain. We further identified a G-->T point mutation in the genomic OB-R sequence in db/db mice. This mutation generates a donor splice site that converts the 106 nt region to a novel exon retained in the OB-R transcript. We predict that the long intracellular domain form of OB-R is crucial for initiating intracellular signal transduction, and as a corollary, the inability to produce this form of OB-R leads to the severe obese phenotype found in db/db mice.