Moretti Paolo, Bouwknecht J Adriaan, Teague Ryan, Paylor Richard, Zoghbi Huda Y
Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA.
Hum Mol Genet. 2005 Jan 15;14(2):205-20. doi: 10.1093/hmg/ddi016. Epub 2004 Nov 17.
Rett syndrome (RTT) is an autistic spectrum disorder with a known genetic basis. RTT is caused by loss of function mutations in the X-linked gene MECP2 and is characterized by loss of acquired motor, social and language skills in females beginning at 6-18 months of age. MECP2 mutations also cause non-syndromic mental retardation in males and females, and abnormalities of MeCP2 expression in the brain have been found in autistic spectrum disorders. We studied home-cage behavior and social interactions in a mouse model of RTT (Mecp2(308/Y)) carrying a mutation similar to common RTT causing alleles. Young adult mutant mice showed abnormal home-cage diurnal activity in the absence of motor skill deficits. Nesting, a phenotype related to social behavior, and social interactions were both impaired in these animals. Mecp2(308/Y) mice showed deficits in nest building and decreased nest use. Although there were no differences in aggression or exploration of novel inanimate stimuli, mutant mice took less initiative and were less decisive approaching unfamiliar males and spent less time in close vicinity to them in several social interaction paradigms. The abnormalities of diurnal activity and social behavior in Mecp2(308/Y) mice are reminiscent of the sleep/wake dysfunction and autistic features of RTT. These data suggest that MECP2 regulates the expression and/or function of genes involved in social behavior. The study of Mecp2(308/Y) mice will allow the identification of the molecular basis of social impairment in RTT and related autistic spectrum disorders.
雷特综合征（RTT）是一种具有已知遗传基础的自闭症谱系障碍。RTT由X连锁基因MECP2的功能丧失突变引起，其特征是女性在6至18个月大时出现获得性运动、社交和语言技能丧失。MECP2突变还会导致男性和女性出现非综合征性智力迟钝，并且在自闭症谱系障碍中发现大脑中MeCP2表达异常。我们研究了携带与常见RTT致病等位基因相似突变的RTT小鼠模型（Mecp2(308/Y)）的笼内行为和社交互动。年轻成年突变小鼠在没有运动技能缺陷的情况下表现出异常的笼内昼夜活动。筑巢是一种与社交行为相关的表型，这些动物的筑巢和社交互动均受损。Mecp2(308/Y)小鼠在筑巢方面存在缺陷，且筑巢利用率降低。尽管在对新的无生命刺激的攻击性或探索性方面没有差异，但在几种社交互动范式中，突变小鼠主动接近陌生雄性的积极性较低，决策能力较差，与它们近距离接触的时间也较少。Mecp2(308/Y)小鼠的昼夜活动和社交行为异常让人联想到RTT的睡眠/觉醒功能障碍和自闭症特征。这些数据表明，MECP2调节参与社交行为的基因的表达和/或功能。对Mecp2(308/Y)小鼠的研究将有助于确定RTT及相关自闭症谱系障碍中社交障碍的分子基础。
