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Reduced expression of the ATRX gene, a chromatin‐remodeling factor, causes hippocampal dysfunction in mice
Author(s) -
Nogami Tatsuya,
Beppu Hideyuki,
Tokoro Takashi,
Moriguchi Shigeki,
Shioda Norifumi,
Fukunaga Kohji,
Ohtsuka Toshihisa,
Ishii Yoko,
Sasahara Masakiyo,
Shimada Yutaka,
Nishijo Hisao,
Li En,
Kitajima Isao
Publication year - 2011
Publication title -
hippocampus
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.767
H-Index - 155
eISSN - 1098-1063
pISSN - 1050-9631
DOI - 10.1002/hipo.20782
Subject(s) - atrx , biology , chromatin remodeling , death associated protein 6 , neuroscience , microbiology and biotechnology , mutation , chromatin , genetics , gene , transcription factor , nuclear protein
Mutations of the ATRX gene, which encodes an ATP‐dependent chromatin‐remodeling factor, were identified in patients with α‐thalassemia X‐linked mental retardation (ATR‐X) syndrome. There is a milder variant of ATR‐X syndrome caused by mutations in the Exon 2 of the gene. To examine the impact of the Exon 2 mutation on neuronal development, we generated ATRX mutant ( ATRX Δ E2 ) mice. Truncated ATRX protein was produced from the ATRX Δ E2 mutant allele with reduced expression level. The ATRX Δ E2 mice survived and reproduced normally. There was no significant difference in Morris water maze test between wild‐type and ATRX Δ E2 mice. In a contextual fear conditioning test, however, total freezing time was decreased in ATRX Δ E2 mice compared to wild‐type mice, suggesting that ATRX Δ E2 mice have impaired contextual fear memory. ATRX Δ E2 mice showed significantly reduced long‐term potentiation in the hippocampal CA1 region evoked by high‐frequency stimulation. Moreover, autophosphorylation of calcium‐calmodulin‐dependent kinase II (αCaMKII) and phosphorylation of glutamate receptor, ionotropic, AMPA 1 (GluR1) were decreased in the hippocampi of the ATRX Δ E2 mice compared to wild‐type mice. These findings suggest that ATRX Δ E2 mice may have fear‐associated learning impairment with the dysfunction of αCaMKII and GluR1. The ATRX Δ E2 mice would be useful tools to investigate the role of the chromatin‐remodeling factor in the pathogenesis of abnormal behaviors and learning impairment. © 2010 Wiley‐Liss, Inc.

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