Karthigasan J, Evans E L, Vouyiouklis D A, Inouye H, Borenshteyn N, Ramamurthy G V, Kirschner D A
Neurology Research, Children's Hospital, Massachusetts, USA.
J Neurochem. 1996 Jan;66(1):338-45. doi: 10.1046/j.1471-4159.1996.66010338.x.
Myelinated CNS tissues from homozygous/hemizygous and heterozygous jimpy rumpshaker jprsh mutant mice were examined to determine the consequences on myelin structure of this mutation in the proteolipid protein (PLP) gene. Polyacrylamide gel electrophoresis and immunoblotting of brain homogenates confirmed that there was a decrease in PLP levels on the B6C3 genetic background onto which this gene was bred. We also observed an increase in level of a protein band that could correspond to the uncharacterized 10-kDa PLP previously reported in jprsh mice on an Rb(1.3) 1Bnr background. High-performance TLC and densitometry of lipids from brain homogenate and isolated myelin revealed a decrease in content of cerebrosides and sulfatides. Electron microscopy on optic nerves revealed that normal radial component is retained in jprsh myelin, further substantiating that PLP is not a component of this junctional complex. X-ray diffraction measurements on unfixed optic nerves showed that the jprsh period is 5-10 A larger than normal. Moreover, jprsh optic nerve myelin was unstable, as evidenced by a continual increase in the period postdissection. jprsh myelin that was equilibrated at varying pH and ionic strength typically had a larger than normal period under all conditions (both swelling and compacting). Our findings thus demonstrate that the biochemical abnormalities in the jprsh mutant correlate with a wider periodicity and less stable packing of the myelin.
对纯合/半合子和杂合子的跳跃性震颤（jimpy rumpshaker，jprsh）突变小鼠的有髓鞘中枢神经系统组织进行检查，以确定该蛋白脂蛋白（PLP）基因突变对髓鞘结构的影响。对脑匀浆进行聚丙烯酰胺凝胶电泳和免疫印迹分析，证实了在该基因所转入的B6C3遗传背景下，PLP水平降低。我们还观察到一条蛋白带的水平增加，该蛋白带可能对应于先前在Rb(1.3) 1Bnr背景的jprsh小鼠中报道的未鉴定的10 kDa PLP。对脑匀浆和分离的髓鞘中的脂质进行高效薄层层析和光密度测定，结果显示脑苷脂和硫脂的含量降低。对视神经进行电子显微镜检查发现，jprsh髓鞘中保留了正常的放射状成分，进一步证实PLP不是这种连接复合体的组成部分。对未固定的视神经进行X射线衍射测量表明，jprsh周期比正常周期大5-10 Å。此外，jprsh视神经髓鞘不稳定，解剖后周期持续增加即证明了这一点。在不同pH和离子强度下平衡的jprsh髓鞘在所有条件下（肿胀和压实）通常都具有比正常更大的周期。因此，我们的研究结果表明，jprsh突变体中的生化异常与髓鞘更宽的周期性和更不稳定的堆积相关。
