Retinal degeneration but not obesity is observed in null mutants of the tubby-like protein 1 gene
Retinal degeneration but not obesity is observed in null mutants of the tubby-like protein 1 gene
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DOI：
10.1093/hmg/9.2.155
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发表时间：
2000-01-22
影响因子：
3.5
通讯作者：
Duyao, MP
中科院分区：
文献类型：
--
作者：
Ikeda, S;Shiva, N;Duyao, MP
tub基因是一个功能未知的保守的神经元基因家族的成员。该基因的突变会导致早发性失明和耳聋，以及迟发性肥胖和胰岛素抵抗。为了验证这一假设，即该基因家族的其他成员内的突变将导致在tubby小鼠中观察到的相似表型，因此具有相似的功能特性，我们通过同源重组产生了tubby样蛋白（Tulp）1基因的无效突变体。与tubby小鼠相似，Tulp 1（-/-）小鼠表现出早发性视网膜变性，伴有进行性、快速的光感受器丧失，进一步支持了先前鉴定的人类TULP 1基因突变确实是视网膜色素变性的病因的观点。然而，与tubby小鼠相反，Tulp 1（-/-）小鼠表现出正常的听力能力，并且令人惊讶的是，尽管事实上TUB和TULP 1都在下丘脑内已知参与进食行为和能量稳态的区域中的相同神经元中表达，但TUB和TULP 1在这些神经元的核中显示出明显不同的染色模式，这也许可以解释Tulp 1（-/-）和tubby突变小鼠之间体重的差异。
The tub gene is a member of a small, well conserved neuronal gene family of unknown function. Mutations within this gene lead to early-onset blindness and deafness, as well as late-onset obesity and insulin resistance. To test the hypothesis that mutations within other members of this gene family would lead to similar phenotypes as observed in tubby mice, and hence have similar functional properties, we have generated null mutants of the tubby-like protein (Tulp) 1 gene by homologous recombination. Similarly to tubby mice, Tulp1(-/-) mice exhibit an early-onset retinal degeneration with a progressive, rapid loss of photoreceptors, further supporting the notion that previously identified mutations within the human TULP1 gene are indeed causative of retinitis pigmentosa. However, in contrast to tubby mice, Tulp1(-/-) mice exhibited normal hearing ability and, surprisingly, normal body weight despite the fact that both TUB and TULP1 are expressed in the same neurons within the hypothalamus in areas known to be involved in feeding behavior and energy homeo stasis, However, TUB and TULP1 show a distinctly different staining pattern in the nucleus of these neurons, perhaps explaining the difference in body weight between the Tulp1(-/-) and tubby mutant mice.