Reduced exploration, increased anxiety, and altered social behavior: Autistic-like features of euchromatin histone methyltransferase 1 heterozygous knockout mice

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• 作者：Monique C.M. Balemans ; Manon M.H. Huibers ; Nathalie W.D. Eikelenboom ; Arthur J. Kuipers ; Rik C.J. van Summeren ; Michael M.C.A. Pijpers ; Makoto Tachibana ; Yoichi Shinkai ; Hans van Bokhoven ; Catharina E
• 关键词：Euchromatin histone methyltransferase 1 ; GLP ; Knockout mouse ; Mental retardation ; Autism ; Exploration ; Anxiety ; Social interaction
• 刊名：Behavioural Brain Research
• 出版年：2010
• 出版时间：17 March 2010
• 年：2010
• 卷：208
• 期：1
• 页码：47-55
• 全文大小：320 K

文摘

The 9q34.3 subtelomeric deletion syndrome is a newly defined mental retardation syndrome, caused by haplo-insufficiency of the euchromatin histone methyltransferase 1 (EHMT1) gene. Patients also have childhood hypotonia, facial dysmorphisms, delay in reaching developmental milestones, and behavioral problems like aggressive outbursts, hypoactivity, or autistic-like features. Male and female heterozygous Ehmt1 knockout mice (Ehmt1^+/−, aged 1–20 months, kept on a C57BL/6J background), were used to investigate whether they mimic the patients behavioral characteristics by comparing their behavior to wildtype littermates. The Ehmt1^+/− mice revealed reduced activity and exploration, with increased anxiety compared to wildtype mice when exposed to novel environments in the open field, object exploration, marble burying, light-dark box, mirrored chamber and T-maze tests. They also demonstrated diminished social play when encountering a mouse from a different litter, and a delayed or absent response to social novelty when exposed to a stranger mouse. However, no differences in phenotyper home cage locomotor activity or rotarod motor function were observed between Ehmt1^+/− and wildtype mice. Together, these results indicate that the hypoactivity and the autistic-like features of 9q34.3 subtelomeric deletion syndrome patients are recapitulated in this Ehmt1^+/− mouse model, and that the hypoactivity is apparently not caused by any motor dysfunction. Together, these observations make it plausible that the Ehmt1^+/− mouse is a faithful mammalian model for the autistic-like behavioral features of patients with the 9q34.3 subtelomeric deletion syndrome.