UC Riverside

Fragile X Syndrome (FXS) is an inherited X-linked neurodevelopmental disorder associated with intellectual disability, sensory processing abnormalities and is one of the leading genetic causes of autism. FXS is a monogenic disorder caused by expansion of CGG repeats in the 5'-untranslated area of the Fragile X Messenger Ribonucleoprotein 1 (Fmr1) gene, leading to a loss of its product, Fragile X Messenger Ribonucleoprotein (FMRP). Therefore, Fmr1 knock-out mice are utilized as mouse models of FXS that demonstrate similar FXS-related behavioral phenotypes, including hyperexcitability and anxiety. While cell specific mechanisms implicated in the abnormal behaviors are still under investigation, a previous study suggested that astrocytes may contribute to these deficits. In this study we tested the effects of astrocyte-specific deletion of Fmr1 gene during postnatal day (P)14-P28 developmental period on mouse behaviors. For this, we crossed floxed Fmr1 mice with GFAP-ERT2-Cre mouse line. Astrocyte-specific Fmr1 deletion was induced in astrocytes with tamoxifen at P14 and behaviors were tested at P28. We used an open field test and elevated plus maze test to measure hyperactivity and anxiety-like behaviors. Social preference and sociability were tested using a three-chamber test. We found that these mice exhibited FXS-associated behaviors such as hyperactivity and anxiety-like behaviors in the open field with no sex differences. We also observed some differences in social preference and sociability between WT and cKO mice. Our findings suggest that timing of Fmr1 deletion from astrocytes may differentially affect neuronal activity in different brain areas, which could explain the difference in behavioral phenotypes.