Cammer W, Zhang H, Tansey F A
Department of Neurology, Albert Einstein College of Medicine, Bronx, New York 10461, USA.
J Neurosci Res. 1995 Mar 1;40(4):451-7. doi: 10.1002/jnr.490400404.
In the choroid plexus carbonic anhydrase II (CAII) supports the transport of bicarbonate ions, sodium ions, and water from blood to the CSF, and in the myelin sheath CAII supports compaction of myelin by stimulating cotransport of ions and water out from between the myelin membranes. In view of the latter, it is surprising that mutant mice deficient in CAII (Car-2n) have compact myelin. Since myelin basic protein also takes part in myelin compaction, we bred double CAII-deficient, myelin-deficient (Mld) mutant mice, in which the adults would have some compact myelin sheaths and a partial deficiency in myelin basic protein, with a view to examining oligodendrocytes and myelin sheaths in the double mutant. Like the parent Mld strain, the double mutants displayed tremors and seizures; however, the onset of seizures was delayed significantly in the double mutants, and the lifespan increased by several months. Like the brains of Car-2n mutants, those of double mutants (MldCar-2n) were deficient in mRNA and protein for CAII and showed upregulation of a different isozyme, CAIV. In the double mutants, oligodendrocytes were reduced in number, and the myelin sheaths and oligodendrocytes were swollen. The partial protection against seizures, which CAII deficiency conferred, suggests that acidosis in the central nervous system (CNS) of the Car-2n and MldCar-2n mice, due to absence of CAII from the choroid plexus, may downregulate the activity of NMDA receptors.(ABSTRACT TRUNCATED AT 250 WORDS)
在脉络丛中，碳酸酐酶II（CAII）支持碳酸氢根离子、钠离子和水从血液向脑脊液的转运；在髓鞘中，CAII通过刺激离子和水从髓鞘膜之间共转运出去来支持髓鞘的压实。鉴于后者，缺乏CAII的突变小鼠（Car-2n）具有紧密的髓鞘这一点令人惊讶。由于髓鞘碱性蛋白也参与髓鞘压实，我们培育了双缺失CAII和髓鞘（Mld）的突变小鼠，成年后这些小鼠会有一些紧密的髓鞘和髓鞘碱性蛋白部分缺乏，目的是检查双突变体中的少突胶质细胞和髓鞘。与亲本Mld品系一样，双突变体表现出震颤和癫痫发作；然而，双突变体中癫痫发作的起始明显延迟，寿命延长了几个月。与Car-2n突变体的大脑一样，双突变体（MldCar-2n）的大脑缺乏CAII的mRNA和蛋白质，并显示出另一种同工酶CAIV的上调。在双突变体中，少突胶质细胞数量减少，髓鞘和少突胶质细胞肿胀。CAII缺乏所赋予的对癫痫发作的部分保护表明，由于脉络丛中缺乏CAII，Car-2n和MldCar-2n小鼠中枢神经系统（CNS）中的酸中毒可能会下调NMDA受体的活性。（摘要截短于250字）
