Biochemical analysis of myelin proteins in a novel neurological mutant: the taiep rat.
Biochemical analysis of myelin proteins in a novel neurological mutant: the taiep rat.
复制标题
对一种新型神经突变体：taiep 大鼠的髓磷脂蛋白进行生化分析。
DOI：
10.1046/j.1471-4159.1997.69020773.x
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发表时间：
1997
影响因子：
4.7
通讯作者：
Duncan,ID
中科院分区：
文献类型：
--
作者：
Möller,JR;Durr,PG;Quarles,RH;Duncan,ID
从1天至16个月龄的taiep、携带者和对照大鼠中取出半球、脊髓和坐骨神经。从中枢神经系统taep组织的绝对髓鞘产量达到高峰，在12个月，然后下降，直到他们达到一个低的，但稳定的水平。受影响半球的髓鞘产量表示为年龄匹配对照的百分比，从2周开始持续下降，直至达到10%-15%的稳定水平。脊髓也是如此，但在这里，髓鞘产量达到了一个略高的20- 25%的百分比平台。与对照组大鼠相比，从受影响的大鼠分离的CNS髓鞘组分具有更高的高分子量蛋白质含量。CNS匀浆的Western印迹分析显示，髓鞘碱性蛋白（MBP）、蛋白脂质蛋白和2′，3 ′-环核苷酸3′-磷酸二酯酶均存在，但降低至与髓鞘缺乏一致的水平。然而，髓鞘相关糖蛋白（MAG）水平的降低总是比其他三种髓鞘蛋白的降低多得多，并且在年轻时，MAG的表观分子量在突变体中增加。坐骨神经匀浆的蛋白质印迹分析表明，MBP，MAG和P0的水平在对照组和突变动物中没有显着差异。这些结果表明CNS的早期髓鞘形成不足，在2个月时髓鞘达到峰值水平，随后是长时间的髓鞘丢失，直到达到非常低但稳定的髓鞘水平。与其他CNS髓鞘蛋白质相比，MAG的持续更大的损失与大多数其他髓鞘生成不足突变体不同，其中MAG与致密髓鞘蛋白质相比相对保留。这可能是由于taiep突变体中的微管异常干扰髓鞘蛋白的转运，并且由于其在轴周少突胶质细胞膜中的最远端位置而对MAG具有最大的影响。
Hemispheres, spinal cords, and sciatic nerves were taken from taiep, carrier, and control rats at ages ranging from 1 day to 16 months. Absolute myelin yields from CNS taiep tissues peaked at ∼2 months and then decreased until they reached a low but stable level. Myelin yield from the affected hemispheres expressed as a percentage of age‐matched controls decreased continuously from 2 weeks until it reached a stable level of ∼10–15%. The same was true for the spinal cords, but here the myelin yield reached a plateau at a slightly higher percentage of 20–25%. In comparison with control rats, isolated CNS myelin fractions from the affected rats had a greater content of high molecular weight proteins. Western blot analyses of CNS homogenates revealed that myelin basic protein (MBP), proteolipid protein, and 2′,3′‐cyclic nucleotide 3′‐phosphodiesterase were all present but decreased to levels generally consistent with the deficiencies of myelin. However myelin‐associated glycoprotein (MAG) levels always were reduced much more than those of the other three myelin proteins, and at younger ages the apparent molecular weight for MAG was increased in the mutants. Western blot analyses of sciatic nerve homogenates showed that the levels of MBP, MAG, and P0were not significantly different in control and mutant animals. These results suggested an early hypomyelination of the CNS, with peak levels of myelin at 2 months, followed by a prolonged period of myelin loss, until a very low but stable myelin level was reached. The consistently greater loss of MAG, in comparison with other CNS myelin proteins, is different from most other hypomyelinating mutants in which MAG is relatively preserved in comparison with the proteins of compact myelin. This might be due to microtubular abnormalities in the taiep mutant interfering with transport of myelin proteins and having the greatest effect on MAG because of its most distal location in the periaxonal oligodendroglial membranes.