Fragile X Syndrome (FXS) is a genetic disorder caused by a CGG expansion in the Fmr1 gene. This condition tends to affect males more severely, while females often present a mosaic pattern of effects. Symptoms of FXS include: delayed crawling and walking, speech delays, hyperactivity & impulsivity, and cognitive deficits.
Mice with a knockout allele of the Fmr1 gene on the X chromosome exhibit phenotypic characteristics of FXS in humans. Male Fmr1 knockout mice, particularly those bred on an FVB/n background at PsychoGenics, are a valuable tool for exploring the mechanisms of Fragile X syndrome.
Increased Locomotor Activity
Increased distance traveled in the open field arena observed with Fmr1 KO mice vs. WT.
Deficits in Fear Conditioning
Fmr1 KO show cognitive deficits in the cue fear conditioning test, as seen in the decreased freezing response.
Tonic Inhibitory Currents Reduced in Dentate Granule Cells
Tonic inhibitory currents were significantly decreased in dentate gyrus of Fmr1 KO mice. In the presence or absence of THIP, a GABAA receptor agonist that preferentially activates tonic currents in neurons by binding to the delta-subunit containing GABAA receptors.
Enhanced Hippocampal mGluR-dependent long-term depression (LTD)
Fmr1 KO mice exhibit decreased hippocampal mGluR-dependent LTD, which is reversed by mGluR antagonist 8-OH-DPAT.
Increased Hippocampal BDNF Levels
