Efhc1 deficiency causes spontaneous myoclonus and increased seizure susceptibility
Efhc1 deficiency causes spontaneous myoclonus and increased seizure susceptibility
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DOI：
10.1093/hmg/ddp006
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发表时间：
2009-03-15
影响因子：
3.5
通讯作者：
Yamakawa, Kazuhiro
中科院分区：
文献类型：
--
作者：
Suzuki, Toshimitsu;Miyamoto, Hiroyuki;Yamakawa, Kazuhiro
EFHC 1基因突变在癫痫患者中已有报道，包括青少年肌阵挛性癫痫患者。Myoclonin 1，也称为mRib 72 -1，由小鼠Efhc 1基因编码。Myoclonin 1主要表达于胚胎脉络丛、生后室管膜纤毛、气管纤毛和精子鞭毛。在这项研究中，我们产生了存活的Efhc 1缺陷小鼠。大多数小鼠的外观正常，并且发现两性都能生育。然而，脑室显着扩大的无效突变体，但不是在杂合子。虽然纤毛结构被发现是完整的，纤毛跳动频率显着降低无效突变体。在成年阶段，杂合和无效突变体发生频繁的自发性肌阵挛。此外，戊四氮诱导癫痫发作的阈值显着降低杂合和无效突变体。这些观察结果似乎进一步表明，肌细胞分裂素1功能的减少或丧失可能是EFHC 1突变引起癫痫的分子基础。
Mutations in EFHC1 gene have been previously reported in patients with epilepsies, including those with juvenile myoclonic epilepsy. Myoclonin1, also known as mRib72-1, is encoded by the mouse Efhc1 gene. Myoclonin1 is dominantly expressed in embryonic choroid plexus, post-natal ependymal cilia, tracheal cilia and sperm flagella. In this study, we generated viable Efhc1-deficient mice. Most of the mice were normal in outward appearance, and both sexes were found to be fertile. However, the ventricles of the brains were significantly enlarged in the null mutants, but not in the heterozygotes. Although the ciliary structure was found intact, the ciliary beating frequency was significantly reduced in null mutants. In adult stages, both the heterozygous and null mutants developed frequent spontaneous myoclonus. Furthermore, the threshold of seizures induced by pentylenetetrazol was significantly reduced in both heterozygous and null mutants. These observations seem to further suggest that decrease or loss of function of myoclonin1 may be the molecular basis for epilepsies caused by EFHC1 mutations.