Suter U, Welcher A A, Ozcelik T, Snipes G J, Kosaras B, Francke U, Billings-Gagliardi S, Sidman R L, Shooter E M
Department of Neurobiology, Stanford University School of Medicine, California 94305.
Nature. 1992 Mar 19;356(6366):241-4. doi: 10.1038/356241a0.
The autosomal dominant trembler mutation (Tr), maps to mouse chromosome 11 (ref. 2) and manifests as a Schwann-cell defect characterized by severe hypomyelination and continuing Schwann-cell proliferation throughout life. Affected animals move clumsily and develop tremor and transient seizures at a young age. We have recently described a potentially growth-regulating myelin protein, peripheral myelin protein-22 (PMP-22; refs 7, 8), which is expressed by Schwann cells and found in peripheral myelin. We now report the assignment of the gene for PMP-22 to mouse chromosome 11. Cloning and sequencing of PMP-22 complementary DNAs from inbred Tr mice reveals a point mutation that substitutes an aspartic acid residue for a glycine in a putative membrane-associated domain of the PMP-22 protein. Our results identify the PMP-22 gene as a likely candidate for the mouse trembler locus and will encourage the search for mutations in the corresponding human gene in pedigrees with hypertrophic neuropathies such as Charcot-Marie-Tooth and Dejerine-Sottas diseases (hereditary motor and sensory neuropathies I and III).
常染色体显性震颤突变（Tr）定位于小鼠11号染色体（参考文献2），表现为施万细胞缺陷，其特征为严重的髓鞘形成不足以及施万细胞终生持续增殖。患病动物行动笨拙，幼年时会出现震颤和短暂性癫痫发作。我们最近描述了一种可能具有生长调节作用的髓磷脂蛋白，即外周髓磷脂蛋白-22（PMP-22；参考文献7、8），它由施万细胞表达并存在于外周髓磷脂中。我们现在报告PMP-22基因定位于小鼠11号染色体。从近交系Tr小鼠中克隆并测序PMP-22互补DNA，发现一个点突变，该突变在PMP-22蛋白的一个假定膜相关结构域中用一个天冬氨酸残基替代了一个甘氨酸残基。我们的结果确定PMP-22基因为小鼠震颤基因座的一个可能候选基因，并将促使人们在患有诸如夏科-马里-图思病和德热里纳-索塔斯病（遗传性运动和感觉神经病I型和III型）等肥厚性神经病的家系中寻找相应人类基因的突变。
