Modifying behavioral phenotypes in Fmr1KO mice: genetic background differences reveal autistic-like responses.
Fragile X syndrome (FXS) is the most common inherited form of intellectual disability in humans. In addition to cognitive impairment, patients may exhibit hyperactivity, attention deficits, social difficulties and anxiety, and autistic-like behaviors. The degree to which patients display these behaviors varies considerably and is influenced by family history, suggesting that genetic modifiers play a role in the expression of behaviors in FXS. Several studies have examined behavior in a mouse model of FXS in which the Fmr1 gene has been ablated. Most of those studies were done in Fmr1 knockout mice on a pure C57BL/6 or FVB strain background. To gain a better understanding of the effects of genetic background on behaviors resulting from the loss of Fmr1 gene expression, we generated F1 hybrid lines from female Fmr1 heterozygous mice on a pure C57BL/6J background bred with male Fmr1 wild-type (WT) mice of various background strains (A/J, DBA/2J, FVB/NJ, 129S1/SvImJ and CD-1). Male Fmr1 knockout and WT littermates from each line were examined in an extensive behavioral test battery. Results clearly indicate that multiple behavioral responses are dependent on genetic background, including autistic-like traits that are present on limited genetic backgrounds. This approach has allowed us to identify improved models for different behavioral symptoms present in FXS including autistic-like traits.
Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas 77030, USA.
Corinne M
CM
Spencer
Olga
O
Alekseyenko
Shannon M
SM
Hamilton
Alexia M
AM
Thomas
Ekaterina
E
Serysheva
Lisa A
LA
Yuva-Paylor
Richard
R
Paylor
D000818:Animals; D000831:Animals, Newborn / Q000235:genetics; D002648:Child; D002659:Child Development Disorders, Pervasive / Q000235:genetics*; D004252:DNA Mutational Analysis; D004195:Disease Models, Animal; D005106:Exploratory Behavior; D005260:Female; D051860:Fragile X Messenger Ribonucleoprotein 1 / Q000235:genetics*; D005600:Fragile X Syndrome / Q000235:genetics*; D006580:Genetic Carrier Screening; D005838:Genotype; D006801:Humans; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009043:Motor Activity / Q000235:genetics; D009048:Motor Skills; D010641:Phenotype; D011597:Psychomotor Performance; D055139:Sensory Gating / Q000235:genetics; D012919:Social Behavior; D013239:Stereotyped Behavior
D051860:Fragile X Messenger Ribonucleoprotein 1; C497684:Fmr1 protein, mouse
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