Social Behavior in Fmr1 Knockout Mice Carrying a Human FMR1 Transgene

Fragile X syndrome (FXS) results from the loss of expression of the fragile X mental retardation ( FMR1 ) gene. Individuals affected by FXS experience many behavioral problems, including cognitive impairment, hyperactivity, social anxiety, and autistic-like behaviors. A mouse model of Fmr1 deficiency ( Fmr1 KO) exhibits several similar behavioral phenotypes, including alterations in social behavior. In an earlier study, Fmr1 knockout mice carrying a yeast-artificial chromosome (YAC) transgene that overexpresses normal human FMRP (KOYAC) showed a correction or overcorrection of some behavioral responses, such as hyperactivity and anxiety-related responses. This report presents results from a study examining transgenic rescue of abnormal social responses in Fmr1 KO mice. Relative to their wild-type (WT) littermates, Fmr1 KO mice made more active social approaches to standard C57BL/6 partner mice in a direct social interaction test, a result consistent with a previous study. KOYAC mice showed fewer active approaches to partners than the WT or Fmr1 KO littermates, indicating correction of this phenotype. This finding expands the number of murine behavioral responses caused by Fmr1 deficiency and corrected by overexpression of human FMRP.