Spongiform degeneration in mahoganoid mutant mice
Spongiform degeneration in mahoganoid mutant mice
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DOI：
10.1126/science.1079694
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发表时间：
2003-01-31
期刊：
影响因子：
56.9
通讯作者：
Gunn, TM
中科院分区：
文献类型：
--
作者：
He, L;Lu, XY;Gunn, TM
Mahoganoid是一种小鼠毛色突变，其色素表型和遗传相互作用类似于Attractin（Atrn）。Atrn突变也会导致海绵状神经变性。在这里，我们表明，一个无效突变的mahoganoid导致类似的年龄依赖性神经病理学，包括朊病毒疾病的许多功能，但没有积累的蛋白酶抗性朊病毒蛋白。该基因突变的Mahoganoid编码的RING蛋白在体外具有E3泛素连接酶活性。在表型，表达和遗传相互作用的相似性表明，mahoganoid和Atrn基因是一个保守的调节蛋白质周转的途径，其功能是必不可少的神经元活力的一部分。
mahoganoid is a mouse coat-color mutation whose pigmentary phenotype and genetic interactions resemble those of Attractin (Atrn). Atrn mutations also cause spongiform neurodegeneration. Here, we show that a null mutation for mahoganoid causes a similar age-dependent neuropathology that includes many features of prion diseases but without accumulation of protease-resistant prion protein. The gene mutated in mahoganoid encodes a RING-containing protein with E3 ubiquitin ligase activity in vitro. Similarities in phenotype, expression, and genetic interactions suggest that mahoganoid and Atrn genes are part of a conserved pathway for regulated protein turnover whose function is essential for neuronal viability.