Mice lacking the kf-1 gene exhibit increased anxiety- but not despair-like behavior

Atsushi Tsujimura, Masato Matsuki, Keizo Takao, Kiyofumi Yamanishi, Tsuyoshi Miyakawa, Tamotsu Hashimoto-Gotoh

Research output: Contribution to journalArticle

24 Citations (Scopus)

Abstract

KF-1 was originally identified as a protein encoded by human gene with increased expression in the cerebral cortex of a patient with Alzheimer's disease. In mouse brain, kf-1 mRNA is detected predominantly in the hippocampus and cerebellum, and kf-1 gene expression is elevated also in the frontal cortex of rats after chronic antidepressant treatments. KF-1 mediates E2-dependent ubiquitination and may modulate cellular protein levels as an E3 ubiquitin ligase, though its target proteins are not yet identified. To elucidate the role of kf-1 in the central nervous system, we generated kf-1 knockout mice by gene targeting, using Cre-lox recombination. The resulting kf-1-/- mice were normal and healthy in appearance. Behavioral analyses revealed that kf-1-/- mice showed significantly increased anxiety-like behavior compared with kf-1+/+ littermates in the light/dark transition and elevated plus maze tests; however, no significant differences were observed in exploratory locomotion using the open field test or in behavioral despair using the forced swim and tail suspension tests. These observations suggest that KF-1 suppresses selectively anxiety under physiological conditions probably through modulating protein levels of its unknown target(s). Interestingly, kf-1-/- mice exhibited significantly increased prepulse inhibition, which is usually reduced in human schizophrenic patients. Thus, the kf-1-/- mice provide a novel animal model for elucidating molecular mechanisms of psychiatric diseases such as anxiety/depression, and may be useful for screening novel anxiolytic/antidepressant compounds.

Original languageEnglish
Article number4
JournalFrontiers in Behavioral Neuroscience
Volume2
Issue numberSEP
DOIs
Publication statusPublished - 08-09-2008

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Anxiety
Genes
Antidepressive Agents
Proteins
Hindlimb Suspension
Ubiquitin-Protein Ligases
Gene Targeting
Ubiquitination
Anti-Anxiety Agents
Frontal Lobe
Locomotion
Knockout Mice
Cerebral Cortex
Cerebellum
Genetic Recombination
Psychiatry
Hippocampus
Alzheimer Disease
Central Nervous System
Animal Models

All Science Journal Classification (ASJC) codes

  • Neuropsychology and Physiological Psychology
  • Cognitive Neuroscience
  • Behavioral Neuroscience

Cite this

Tsujimura, Atsushi ; Matsuki, Masato ; Takao, Keizo ; Yamanishi, Kiyofumi ; Miyakawa, Tsuyoshi ; Hashimoto-Gotoh, Tamotsu. / Mice lacking the kf-1 gene exhibit increased anxiety- but not despair-like behavior. In: Frontiers in Behavioral Neuroscience. 2008 ; Vol. 2, No. SEP.
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Mice lacking the kf-1 gene exhibit increased anxiety- but not despair-like behavior. / Tsujimura, Atsushi; Matsuki, Masato; Takao, Keizo; Yamanishi, Kiyofumi; Miyakawa, Tsuyoshi; Hashimoto-Gotoh, Tamotsu.

In: Frontiers in Behavioral Neuroscience, Vol. 2, No. SEP, 4, 08.09.2008.

Research output: Contribution to journalArticle

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