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Mice Lacking the kf-1 Gene Exhibit Increased Anxiety- but not Despair-Like Behavior

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 front...

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Autores principales: Tsujimura, Atsushi, Matsuki, Masato, Takao, Keizo, Yamanishi, Kiyofumi, Miyakawa, Tsuyoshi, Hashimoto-Gotoh, Tamotsu
Formato: Texto
Lenguaje:English
Publicado: Frontiers Research Foundation 2008
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2567108/
https://www.ncbi.nlm.nih.gov/pubmed/18958194
http://dx.doi.org/10.3389/neuro.08.004.2008
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author Tsujimura, Atsushi
Matsuki, Masato
Takao, Keizo
Yamanishi, Kiyofumi
Miyakawa, Tsuyoshi
Hashimoto-Gotoh, Tamotsu
author_facet Tsujimura, Atsushi
Matsuki, Masato
Takao, Keizo
Yamanishi, Kiyofumi
Miyakawa, Tsuyoshi
Hashimoto-Gotoh, Tamotsu
author_sort Tsujimura, Atsushi
collection PubMed
description 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.
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spelling pubmed-25671082008-10-27 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 Front Behav Neurosci Neuroscience 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. Frontiers Research Foundation 2008-09-08 /pmc/articles/PMC2567108/ /pubmed/18958194 http://dx.doi.org/10.3389/neuro.08.004.2008 Text en Copyright © 2008 Tsujimura, Matsuki, Takao, Yamanishi, Miyakawa and Hashimoto-Gotoh. http://www.frontiersin.org/licenseagreement This is an open-access article subject to an exclusive license agreement between the authors and the Frontiers Research Foundation, which permits unrestricted use, distribution, and reproduction in any medium, provided the original authors and source are credited.
spellingShingle Neuroscience
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
title Mice Lacking the kf-1 Gene Exhibit Increased Anxiety- but not Despair-Like Behavior
title_full Mice Lacking the kf-1 Gene Exhibit Increased Anxiety- but not Despair-Like Behavior
title_fullStr Mice Lacking the kf-1 Gene Exhibit Increased Anxiety- but not Despair-Like Behavior
title_full_unstemmed Mice Lacking the kf-1 Gene Exhibit Increased Anxiety- but not Despair-Like Behavior
title_short Mice Lacking the kf-1 Gene Exhibit Increased Anxiety- but not Despair-Like Behavior
title_sort mice lacking the kf-1 gene exhibit increased anxiety- but not despair-like behavior
topic Neuroscience
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2567108/
https://www.ncbi.nlm.nih.gov/pubmed/18958194
http://dx.doi.org/10.3389/neuro.08.004.2008
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