title: Behavioral analysis of male and female Fmr1 knockout mice on C57BL/6 background.
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.
authors.affiliation: Department of Physiology, Michigan State University, East Lansing, MI 48824, USA.
authors.forename: Qi
authors.initials: Q
authors.lastname: Ding
authors.affiliation: Genetics Program, Michigan State University, East Lansing, MI 48824, USA.
authors.forename: Ferzin
authors.initials: F
authors.lastname: Sethna
authors.affiliation: Department of Physiology, Michigan State University, East Lansing, MI 48824, USA; Neuroscience Program, Michigan State University, East Lansing, MI 48824, USA. Electronic address: wangho@msu.edu.
authors.forename: Hongbing
authors.initials: H
authors.lastname: Wang
mesh_terms: D000818:Animals; D001362:Avoidance Learning; D001522:Behavior, Animal; D004195:Disease Models, Animal; D005239:Fear; D005260:Female; D051860:Fragile X Messenger Ribonucleoprotein 1 / Q000235:genetics*; D005600:Fragile X Syndrome / Q000235:genetics / Q000523:psychology*; D006948:Hyperkinesis / Q000235:genetics / Q000523:psychology*; D008297:Male; D008568:Memory; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009043:Motor Activity; D010641:Phenotype; D013216:Reflex, Startle; D012737:Sex Factors
chemical_list: D051860:Fragile X Messenger Ribonucleoprotein 1
keywords: Behavioral phenotypes; Fmr1 knockout mice; Fragile X syndrome; Gender; Genetic background