Mice lacking the schizophrenia-associated protein FEZ1 manifest hyperactivity and enhanced responsiveness to psychostimulants

Nobutaka Sakae, Nobuyuki Yamasaki, Kiyoyuki Kitaichi, Takaichi Fukuda, Mitsunori Yamada, Hiroo Yoshikawa, Takato Hiranita, Yoshiki Tatsumi, Jun Ichi Kira, Tsuneyuki Yamamoto, Tsuyoshi Miyakawa, Keiichi I. Nakayama

研究成果: Contribution to journalArticle査読

45 被引用数 (Scopus)

抄録

FEZ1 (fasciculation and elongation protein zeta 1), a mammalian ortholog of Caenorhabditis elegans UNC-76, interacts with DISC1 (disrupted in schizophrenia 1), a schizophrenia susceptibility gene product, and polymorphisms of human FEZ1 have been associated with schizophrenia. We have now investigated the role of FEZ1 in brain development and the pathogenesis of schizophrenia by generating mice that lack Fez1. Immunofluorescence staining revealed FEZ1 to be located predominantly in γ-aminobutyric acid-containing interneurons. The Fez1-/- mice showed marked hyperactivity in a variety of behavioral tests as well as enhanced behavioral responses to the psychostimulants MK-801 and methamphetamine. In vivo microdialysis revealed that the methamphetamine-induced release of dopamine in the nucleus accumbens was exaggerated in the mutant mice, suggesting that enhanced mesolimbic dopaminergic transmission contributes to their hyperactivity phenotype. These observations implicate impairment of FEZ1 function in the pathogenesis of schizophrenia.

本文言語英語
ページ(範囲)3191-3203
ページ数13
ジャーナルHuman molecular genetics
17
20
DOI
出版ステータス出版済み - 2008

All Science Journal Classification (ASJC) codes

  • 分子生物学
  • 遺伝学
  • 遺伝学(臨床)

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