Mecp2 truncation in male mice promotes affiliative social behavior.

Mouse models of Rett syndrome, with targeted mutations in the Mecp2 gene, show a high degree of phenotypic consistency with the clinical syndrome. In addition to severe and age-specific regression in motor and cognitive abilities, a variety of studies have demonstrated that Mecp2 mutant mice display impaired social behavior. Conversely, other studies indicate complex enhancements of social behavior in Mecp2 mutant mice. Since social behavior is a complicated accumulation of constructs, we performed a series of classic and refined social behavior tasks and revealed a relatively consistent pattern of enhanced pro-social behavior in hypomorphic Mecp2 (308/Y) mutant mice. Analyses of repetitive motor acts, and cognitive stereotypy did not reveal any profound differences due to genotype. Taken together, these results suggest that the mutations associated with Rett syndrome are not necessarily associated with autism-relevant social impairment in mice. However, this gene may be a valuable candidate for revealing basic mechanisms of affiliative behavior.

Motor and cognitive stereotypies in the BTBR T+tf/J mouse model of autism.

The BTBR T+tf/J inbred mouse strain displays a variety of persistent phenotypic alterations similar to those exhibited in autism spectrum disorders (ASDs). The unique genetic background of the BTBR strain is thought to underlie its lack of reciprocal social interactions, elevated repetitive self-directed grooming, and restricted exploratory behaviors. In order to clarify the existence, range, and mechanisms of abnormal repetitive behaviors within BTBR mice, we performed detailed analyses of the microstructure of self-grooming patterns and noted increased overall grooming, higher percentages of interruptions in grooming bouts and a concomitant decrease in the proportion of incorrect sequence transitions compared to C57BL/6J inbred mice. Analyses of active phase home-cage behavior also revealed an increase in stereotypic bar-biting behavior in the BTBR strain relative to B6 mice. Finally, in a novel object investigation task, the BTBR mice exhibited greater baseline preference for specific unfamiliar objects as well as more patterned sequences of sequential investigations of those items. These results suggest that the repetitive, stereotyped behavior patterns of BTBR mice are relatively pervasive and reflect both motor and cognitive mechanisms. Furthermore, other pre-clinical mouse models of ASDs may benefit from these more detailed analyses of stereotypic behavior.