Paranodal junction formation and spermatogenesis require sulfoglycolipids
Paranodal junction formation and spermatogenesis require sulfoglycolipids
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DOI：
10.1073/pnas.032068299
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发表时间：
2002-04-02
影响因子：
11.1
通讯作者：
Taniguchi, N
中科院分区：
文献类型：
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作者：
Honke, K;Hirahara, Y;Taniguchi, N
哺乳动物硫代糖脂包括两个主要成员，硫酸脂（HSO 3 -3-半乳糖基神经酰胺）和硫代糖脂（HSO 3 - 3单半乳糖基烷基酰基甘油）。硫脂是髓鞘的主要脂质成分，并作为众所周知的少突胶质细胞标记抗体O 4的表位。精脂在精母细胞中合成，并在随后的生殖细胞阶段中维持。这两种磺基糖脂都可以通过使用分离的甘草苷磺基转移酶在体外合成。为了研究硫代糖脂的生理作用并确定硫苷脂和精油脂是否通过单一磺基转移酶在体内生物合成，通过基因打靶产生了Cst缺失小鼠。Cst（-/-）小鼠大脑中缺乏硫苷脂，睾丸中缺乏硫苷脂，证明单基因拷贝负责它们的生物合成。CST（-/-）小鼠出生时健康，但在6周龄时开始显示后肢无力，随后显示出明显的震颤和进行性共济失调。虽然致密的髓鞘被保存，Cst（-/-）小鼠表现出异常的结旁连接。另一方面，Cst（-/-）雄性不育，因为在第一次减数分裂前精子发生受阻，而雌性能够繁殖。这些数据表明磺基糖脂在髓鞘功能和精子发生中起关键作用。
Mammalian sulfoglycolipids comprise two major members, sulfaticle (HSO3-3-galactosylceramide) and seminolipid (HSO3-3monogalactosylalkylacylglycerol). Sulfatide is a major lipid component of the myelin sheath and serves as the epitope for the well known oligodendrocyte-marker antibody O4. Seminolipid is synthesized in spermatocytes and maintained in the subsequent germ cell stages. Both sulfoglycolipids can be synthesized in vitro by using the isolated cerebroside sulfotransferase. To investigate the physiological role of sulfoglycolipids and to determine whether sulfatide and seminolipid are biosynthesized in viva by a single sulfotransferase, Cst-null mice were generated by gene targeting. Cst(-/-) mice lacked sulfatide in brain and seminolipid in testis, proving that a single gene copy is responsible for their biosynthesis. Cst(-/-) mice were born healthy, but began to display hindlimb weakness by 6 weeks of age and subsequently showed a pronounced tremor and progressive ataxia. Although compact myelin was preserved, Cst(-/-) mice displayed abnormalities in paranodal junctions. On the other hand, Cst(-/-) males were sterile because of a block in spermatogenesis before the first meiotic division, whereas females were able to breed. These data show a critical role for sulfoglycolipids in myelin function and spermatogenesis.