Abnormalities of social interactions and home-cage behavior in a mouse model of Rett syndrome
Abnormalities of social interactions and home-cage behavior in a mouse model of Rett syndrome
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DOI：
10.1093/hmg/ddi016
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发表时间：
2005-01-15
影响因子：
3.5
通讯作者：
Zoghbi, HY
中科院分区：
文献类型：
--
作者：
Moretti, P;Bouwknecht, JA;Zoghbi, HY
Rett综合征(RTT)是一种具有已知遗传基础的自闭症谱系障碍。RTT是由X连锁基因MECP2的功能突变引起的，其特征是女性在6-18个月大时开始丧失后天获得的运动、社交和语言技能。MeCP2基因突变也会导致男性和女性的非综合征性精神发育迟滞，在自闭症谱系障碍中发现了大脑中MeCP2表达的异常。我们研究了RTT小鼠模型(MeCP2(308/Y))的家庭笼子行为和社会互动，该模型携带与常见RTT引起的等位基因相似的突变。年轻的成年突变小鼠在没有运动技能缺陷的情况下，表现出异常的家庭笼子日活动。在这些动物中，与社会行为相关的表型筑巢和社会互动都受到了损害。MeCP2(308/Y)小鼠在筑巢方面存在缺陷，巢使用减少。尽管在攻击性或探索新的无生命刺激方面没有差异，但在几种社会互动范式中，突变小鼠主动和果断接近陌生雄性的时间更少，与它们亲密接触的时间也更少。MeCP2(308/Y)小鼠的日常活动和社会行为的异常使人联想到RTT的睡眠/觉醒功能障碍和自闭症特征。这些数据表明，MECP2调节参与社会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社会损害和相关自闭症谱系障碍的分子基础。
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.