Efhc1 deficiency causes spontaneous myoclonus and increased seizure susceptibility

Toshimitsu Suzuki, Hiroyuki Miyamoto, Takashi Nakahari, Ikuyo Inoue, Takahiro Suemoto, Bin Jiang, Yuki Hirota, Shigeyoshi Itohara, Takaomi C. Saido, Tadaharu Tsumoto, Kazunobu Sawamoto, Takao K. Hensch, Antonio V. Delgado-Escueta, Kazuhiro Yamakawa

Research output: Contribution to journalArticle

50 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)1099-1109
Number of pages11
JournalHuman Molecular Genetics
Volume18
Issue number6
DOIs
Publication statusPublished - 2009
Externally publishedYes

Fingerprint

Myoclonus
Seizures
Cilia
Epilepsy
Juvenile Myoclonic Epilepsy
Sperm Tail
Pentylenetetrazole
Mutation
Choroid Plexus
Heterozygote
Genes
Brain

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)
  • Molecular Biology

Cite this

Suzuki, T., Miyamoto, H., Nakahari, T., Inoue, I., Suemoto, T., Jiang, B., ... Yamakawa, K. (2009). Efhc1 deficiency causes spontaneous myoclonus and increased seizure susceptibility. Human Molecular Genetics, 18(6), 1099-1109. https://doi.org/10.1093/hmg/ddp006

Efhc1 deficiency causes spontaneous myoclonus and increased seizure susceptibility. / Suzuki, Toshimitsu; Miyamoto, Hiroyuki; Nakahari, Takashi; Inoue, Ikuyo; Suemoto, Takahiro; Jiang, Bin; Hirota, Yuki; Itohara, Shigeyoshi; Saido, Takaomi C.; Tsumoto, Tadaharu; Sawamoto, Kazunobu; Hensch, Takao K.; Delgado-Escueta, Antonio V.; Yamakawa, Kazuhiro.

In: Human Molecular Genetics, Vol. 18, No. 6, 2009, p. 1099-1109.

Research output: Contribution to journalArticle

Suzuki, T, Miyamoto, H, Nakahari, T, Inoue, I, Suemoto, T, Jiang, B, Hirota, Y, Itohara, S, Saido, TC, Tsumoto, T, Sawamoto, K, Hensch, TK, Delgado-Escueta, AV & Yamakawa, K 2009, 'Efhc1 deficiency causes spontaneous myoclonus and increased seizure susceptibility', Human Molecular Genetics, vol. 18, no. 6, pp. 1099-1109. https://doi.org/10.1093/hmg/ddp006
Suzuki T, Miyamoto H, Nakahari T, Inoue I, Suemoto T, Jiang B et al. Efhc1 deficiency causes spontaneous myoclonus and increased seizure susceptibility. Human Molecular Genetics. 2009;18(6):1099-1109. https://doi.org/10.1093/hmg/ddp006
Suzuki, Toshimitsu ; Miyamoto, Hiroyuki ; Nakahari, Takashi ; Inoue, Ikuyo ; Suemoto, Takahiro ; Jiang, Bin ; Hirota, Yuki ; Itohara, Shigeyoshi ; Saido, Takaomi C. ; Tsumoto, Tadaharu ; Sawamoto, Kazunobu ; Hensch, Takao K. ; Delgado-Escueta, Antonio V. ; Yamakawa, Kazuhiro. / Efhc1 deficiency causes spontaneous myoclonus and increased seizure susceptibility. In: Human Molecular Genetics. 2009 ; Vol. 18, No. 6. pp. 1099-1109.
@article{52bc2e88067c43f2bc3d2ea4717672f9,
title = "Efhc1 deficiency causes spontaneous myoclonus and increased seizure susceptibility",
abstract = "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.",
author = "Toshimitsu Suzuki and Hiroyuki Miyamoto and Takashi Nakahari and Ikuyo Inoue and Takahiro Suemoto and Bin Jiang and Yuki Hirota and Shigeyoshi Itohara and Saido, {Takaomi C.} and Tadaharu Tsumoto and Kazunobu Sawamoto and Hensch, {Takao K.} and Delgado-Escueta, {Antonio V.} and Kazuhiro Yamakawa",
year = "2009",
doi = "10.1093/hmg/ddp006",
language = "English",
volume = "18",
pages = "1099--1109",
journal = "Human Molecular Genetics",
issn = "0964-6906",
publisher = "Oxford University Press",
number = "6",

}

TY - JOUR

T1 - Efhc1 deficiency causes spontaneous myoclonus and increased seizure susceptibility

AU - Suzuki, Toshimitsu

AU - Miyamoto, Hiroyuki

AU - Nakahari, Takashi

AU - Inoue, Ikuyo

AU - Suemoto, Takahiro

AU - Jiang, Bin

AU - Hirota, Yuki

AU - Itohara, Shigeyoshi

AU - Saido, Takaomi C.

AU - Tsumoto, Tadaharu

AU - Sawamoto, Kazunobu

AU - Hensch, Takao K.

AU - Delgado-Escueta, Antonio V.

AU - Yamakawa, Kazuhiro

PY - 2009

Y1 - 2009

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=61849107443&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=61849107443&partnerID=8YFLogxK

U2 - 10.1093/hmg/ddp006

DO - 10.1093/hmg/ddp006

M3 - Article

VL - 18

SP - 1099

EP - 1109

JO - Human Molecular Genetics

JF - Human Molecular Genetics

SN - 0964-6906

IS - 6

ER -