Comparative Behavioral Phenotypes of KO, Het, and KO/ Het Mice.

Fragile X syndrome (FXS) is caused by silencing of the gene leading to loss of the protein product fragile X mental retardation protein (FMRP). FXS is the most common monogenic cause of intellectual disability. There are two known mammalian paralogs of FMRP, FXR1P, and FXR2P. The functions of FXR1P and FXR2P and their possible roles in producing or modulating the phenotype observed in FXS are yet to be identified. Previous studies have revealed that mice lacking display similar behavioral abnormalities as knockout (KO) mice. In this study, we expand upon the behavioral phenotypes of KO and (Het) mice and compare them with KO/ Het mice. We find that KO and KO/ Het mice are similarly hyperactive compared to WT and Het mice. KO/ Het mice have more severe learning and memory impairments than KO mice. KO mice display significantly impaired social behaviors compared to WT mice, which are paradoxically reversed in KO/ Het mice. These results highlight the important functional consequences of loss or reduction of FMRP and FXR2P.