A leucine-to-proline mutation in the putative first transmembrane domain of the 22-kDa peripheral myelin protein in the trembler-J mouse.
A leucine-to-proline mutation in the putative first transmembrane domain of the 22-kDa peripheral myelin protein in the trembler-J mouse.
复制标题
trembler-J 小鼠 22 kDa 外周髓磷脂蛋白的假定第一跨膜结构域中亮氨酸到脯氨酸的突变。
DOI：
10.1073/pnas.89.10.4382
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发表时间：
1992
影响因子：
11.1
通讯作者：
Shooter,EM
中科院分区：
文献类型：
--
作者：
Suter,U;Moskow,JJ;Welcher,AA;Snipes,GJ;Kosaras,B;Sidman,RL;Buchberg,AM;Shooter,EM
外周髓鞘蛋白PMP-22是一种潜在的生长调节髓鞘蛋白，由雪旺细胞表达，主要定位于致密的外周髓鞘。近交系震颤(Tr)小鼠的PMP-22基因点突变被发现，并被认为与Tr表型有关，该表型以肢体瘫痪、震颤和一过性癫痫为特征。为了支持这一假说，我们现在报告了PMP-22基因在小鼠11号染色体Tr基因座附近的精细定位。此外，我们在颤抖者-J(TRJ)小鼠的PMP-22基因中发现了第二个点突变，导致PMP-22多肽的第一个跨膜区的亮氨酸残基被Pro残基取代。TRR和TRJ先前被定位为可能的等位基因突变，导致相似但不相同的表型。这一发现与在PMP-22蛋白的物理化学相似区域中发现两个不同的突变是一致的。我们的结果加强了PMP-22基因突变可导致不同形式的周围神经病的假设，并为这些疾病的显性遗传提供了可能的解释线索。
Peripheral myelin protein PMP-22 is a potential growth-regulating myelin protein that is expressed by Schwann cells and predominantly localized in compact peripheral myelin. A point mutation in the Pmp-22 gene of inbred trembler (Tr) mice was identified and proposed to be responsible for the Tr phenotype, which is characterized by paralysis of the limbs as well as tremors and transient seizures. In support of this hypothesis, we now report the fine mapping of the Pmp-22 gene to the immediate vicinity of the Tr locus on mouse chromosome 11. Furthermore, we have found a second point mutation in the Pmp-22 gene of trembler-J (TrJ) mice, which results in the substitution of a leucine residue by a proline residue in the putative first transmembrane region of the PMP-22 polypeptide. Tr and TrJ were previously mapped genetically as possible allelic mutations giving rise to similar, but not identical, phenotypes. This finding is consistent with the discovery of two different mutations in physicochemically similar domains of the PMP-22 protein. Our results strengthen the hypothesis that mutations in the Pmp-22 gene can lead to heterogeneous forms of peripheral neuropathies and offer clues toward possible explanations for the dominant inheritance of these disorders.