CNS myelin and Sertoli cell tight junction strands are absent in Osp/Claudin-11 null mice

CNS myelin and Sertoli cell tight junction strands are absent in Osp/Claudin-11 null mice
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DOI:
10.1016/s0092-8674(00)81553-6
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发表时间:
1999-12-10
期刊:
影响因子:
64.5
通讯作者:
Lazzarini, RA
Lazzarini, RA
中科院分区:
生物学1区
文献类型:
--
作者:
Gow, A;Southwood, CM;Lazzarini, RA

文献摘要

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少突胶质细胞特异性蛋白(OSP)/claudin-11是最近发现的一种在中枢神经系统髓鞘和睾丸中发现的功能未知的跨膜蛋白。在这里,我们证明OSP基因缺失的小鼠表现出神经和生殖缺陷:中枢神经传导减慢,后肢明显虚弱,雄性不育。冷冻断口显示,突变小鼠中枢神经系统髓鞘和支持细胞之间缺乏紧密连接的膜内链。我们的结果表明,OSP是平行排列紧密连接链的媒介,并将其与紧密连接中的其他固有膜蛋白区分开来。这些新的结果直接证明了claudin家族在产生精子发生和正常中枢神经系统功能所必需的紧密连接的细胞旁物理屏障中所起的关键作用。
Oligodendrocyte-specific protein (OSP)/claudin-11 is a recently identified transmembrane protein found in CNS myelin and testis with unknown function. Herein we demonstrate that Osp null mice exhibit both neurological and reproductive deficits: CNS nerve conduction is slowed, hindlimb weakness is conspicuous, and males are sterile. Freeze fracture reveals that tight junction intramembranous strands are absent in CNS myelin and between Sertoli cells of mutant mice. Our results demonstrate that OSP is the mediator of parallel-array tight junction strands and distinguishes this protein from other intrinsic membrane proteins in tight junctions. These novel results provide direct evidence of the pivotal role of the claudin family in generating the paracellular physical barrier of tight junctions necessary for spermatogenesis and normal CNS function.