Edgar J M, McLaughlin M, Barrie J A, McCulloch M C, Garbern J, Griffiths I R
Applied Neurobiology Group, Department of Veterinary Clinical Studies, Institute of Comparative Medicine, University of Glasgow, Bearsden, G61 1QH, Glasgow, Scotland.
Acta Neuropathol. 2004 Apr;107(4):331-5. doi: 10.1007/s00401-003-0808-9. Epub 2004 Jan 24.
The PLP1/Plp gene encodes proteolipid protein (PLP) and DM20, the major central nervous system myelin proteins. Mutations in the PLP1/ Plp gene cause dysmyelinating disorders in man and animals. The rumpshaker mutation was first identified in mice and later linked to a family diagnosed with neurological deficits akin to spastic paraplegia. The dysmyelination in the young rumpshaker mouse is well characterised. Here we report evidence for an age-related increase in myelin due mainly to the myelination of small axons, many large axons remain dysmyelinated. Levels of PLP/DM20 and myelin basic protein are considerably greater in myelin fractions from older compared with younger mutants. Myelin in sheaths of larger axons remains poorly compacted and may account for levels of 2',3'-cyclic nucleotide 3'-phosphodiesterase and myelin-associated glycoprotein being elevated over wild type in older mutant mice. A late-onset distal degeneration of the axons of the longest spinal tract, the fasciculus gracilis, is also noted. This is the first report of Wallerian-type degeneration in mice with spontaneous mutations of the Plp gene.
PLP1/Plp基因编码蛋白脂蛋白（PLP）和DM20，这是中枢神经系统的主要髓鞘蛋白。PLP1/Plp基因突变会导致人和动物的髓鞘形成障碍。“摇臀小鼠”突变最初是在小鼠中发现的，后来与一个被诊断患有类似于痉挛性截瘫的神经功能缺损的家族相关联。幼年“摇臀小鼠”的髓鞘形成障碍特征明显。在此我们报告证据表明，髓鞘随年龄增长而增加，主要是由于小轴突的髓鞘形成，许多大轴突仍存在髓鞘形成障碍。与幼年突变体相比，老年突变体髓鞘组分中PLP/DM20和髓鞘碱性蛋白的水平要高得多。较大轴突髓鞘中的髓鞘仍紧密性较差，这可能是老年突变体小鼠中2',3'-环核苷酸3'-磷酸二酯酶和髓鞘相关糖蛋白水平高于野生型的原因。还注意到最长脊髓束即薄束的轴突出现迟发性远端变性。这是关于Plp基因自发突变小鼠中出现华勒氏型变性的首次报道。
