Mitchell L S, Gillespie S C, McAllister F, Fanarraga M L, Kirkham D, Kelly B, Brophy P J, Griffiths I R, Montague P, Kennedy P G
Department of Veterinary Surgery, University of Glasgow, Scotland.
J Neurosci Res. 1992 Oct;33(2):205-17. doi: 10.1002/jnr.490330204.
Rumpshaker (rsh) is an X-linked mutation causing hypomyelination of the CNS of mice and has recently been identified as an allele of jimpy (jp). The mutation (known as jprsh) differs in several respects from other X-linked myelin mutants, including jp, in that mice have normal longevity, oligodendrocyte numbers are not decreased, and cell death is not a feature. Myelin sheaths are deficient in immunostainable PLP protein. The present study examines the developmental expression of the major myelin protein genes and translatability of PLP and MBP mRNA. Differences between the spinal cord and brain of mutants are evident in that mRNA levels are more markedly decreased in the brain. Protein levels are severely reduced in both locations and to a proportionately greater extent than the mRNA, particularly in the spinal cord where PLP RNA and protein are approximately 80% and 10-20%, respectively, of age-matched wild type mice. DM-20 protein, the other major product of the PLP gene, is disproportionately expressed in rumpshaker as is a 10 kDa proteolipid. In vitro translation studies indicate a marked decrease in PLP translation products from mutant RNA. There is no deficiency in the number of PLP mRNA-expressing oligodendrocytes although the abundance per cell is reduced. The data suggest that the phenotypic effects of the mutation may be associated with reduced translation of major myelin proteins, in particular PLP and its incorporation into compact myelin. However, the mutation is compatible with survival of oligodendrocytes and their differentiation to the stage of expressing PLP/DM-20 mRNA.
摇臀鼠（rsh）是一种X连锁突变，可导致小鼠中枢神经系统髓鞘形成减少，最近被鉴定为震颤鼠（jp）的一个等位基因。该突变体（称为jprsh）在几个方面与其他X连锁髓鞘突变体不同，包括jp，其特点是小鼠寿命正常，少突胶质细胞数量不减少，且不存在细胞死亡现象。髓鞘中可免疫染色的PLP蛋白缺乏。本研究检测了主要髓鞘蛋白基因的发育表达以及PLP和MBP mRNA的可翻译性。突变体脊髓和脑之间的差异很明显，即脑中mRNA水平下降更为显著。两个部位的蛋白水平均严重降低，且降低程度比mRNA更大，尤其是在脊髓中，PLP RNA和蛋白分别约为年龄匹配野生型小鼠的80%和10 - 20%。PLP基因的另一个主要产物DM - 20蛋白在摇臀鼠中表达失调，还有一种10 kDa的蛋白脂质也是如此。体外翻译研究表明，突变体RNA产生的PLP翻译产物显著减少。虽然每个表达PLP mRNA的少突胶质细胞中的PLP mRNA丰度降低，但表达PLP mRNA的少突胶质细胞数量并无不足。数据表明，该突变的表型效应可能与主要髓鞘蛋白翻译减少有关，特别是PLP及其整合到紧密髓鞘中。然而，该突变与少突胶质细胞的存活及其分化到表达PLP/DM - 20 mRNA的阶段是相容的。
