Behavioral analysis of male and female Fmr1 knockout mice on C57BL/6 background

Behav Brain Res. 2014 Sep 1:271:72-8. doi: 10.1016/j.bbr.2014.05.046. Epub 2014 Jun 2.

Abstract

Fragile X syndrome (FXS) is a monogenic disease caused by mutations in the FMR1 gene. The Fmr1 knockout (KO) mice show many aspects of FXS-related phenotypes, and have been used as a major pre-clinical model for FXS. Although FXS occurs in both male and female patients, most studies on the mouse model use male animals. Few studies test whether gender affects the face validity of the mouse model. Here, we examined multiple behavioral phenotypes with male hemizygous and female homozygous Fmr1 KO mice on C57BL/6 background. For each behavioral paradigm, we examined multiple cohorts from different litters. We found that both male and female Fmr1 KO mice displayed significant audiogenic seizures, hyperactivity in the open field test, deficits in passive avoidance and contextual fear memory, and significant enhancement of PPI at low stimulus intensity. Male and female Fmr1 KO mice also showed more transitional movement between the lit and dark chambers in the light-dark tests. The lack of gender effects suggests that the Fmr1 KO mouse is a reasonable tool to test the efficacy of potential FXS therapies.

Keywords: Behavioral phenotypes; Fmr1 knockout mice; Fragile X syndrome; Gender; Genetic background.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Avoidance Learning
  • Behavior, Animal*
  • Disease Models, Animal
  • Fear
  • Female
  • Fragile X Mental Retardation Protein / genetics*
  • Fragile X Syndrome / genetics
  • Fragile X Syndrome / psychology*
  • Hyperkinesis / genetics
  • Hyperkinesis / psychology*
  • Male
  • Memory
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Motor Activity
  • Phenotype
  • Reflex, Startle
  • Sex Factors

Substances

  • Fragile X Mental Retardation Protein