Behavioral Phenotype of Fmr1 Knock-Out Mice during Active Phase in an Altered Light/Dark Cycle.
Fragile X syndrome (FXS) is the most commonly inherited form of intellectual disability and is a disorder that is also highly associated with autism. FXS occurs as a result of an expanded CGG repeat sequence leading to transcriptional silencing. In an animal model of FXS in which Fmr1 is knocked out (Fmr1 KO), many physical, physiological, and behavioral characteristics of the human disease are recapitulated. Prior characterization of the mouse model was conducted during the day, the inactive phase of the circadian cycle. Circadian rhythms are an important contributor to behavior and may play a role in the study of disease phenotype. Moreover, changes in the parameters of circadian rhythm are known to occur in FXS animal models. We conducted an investigation of key behavioral phenotypes in Fmr1 KO mice during their active phase. We report that phase did not alter the Fmr1 KO phenotype in open field activity, anxiety, and learning and memory. There was a slight effect of phase on social behavior as measured by time in chamber, but not by time spent sniffing. Our data strengthen the existing data characterizing the phenotype of Fmr1 KO mice, indicating that it is independent of circadian phase.
Section on Neuroadaptation and Protein Metabolism, Department of Health and Human Services, National Institute of Mental Health, National Institutes of Health , Bethesda, Maryland 20892.
R Michelle
RM
Saré
Section on Neuroadaptation and Protein Metabolism, Department of Health and Human Services, National Institute of Mental Health, National Institutes of Health , Bethesda, Maryland 20892.
Merlin
0000-0001-6326-6672
M
Levine
Section on Neuroadaptation and Protein Metabolism, Department of Health and Human Services, National Institute of Mental Health, National Institutes of Health , Bethesda, Maryland 20892.
Carolyn Beebe
CB
Smith
D000221:Adaptation, Ocular / Q000235:genetics*; D000704:Analysis of Variance; D000818:Animals; D001007:Anxiety / Q000209:etiology / Q000235:genetics; D001362:Avoidance Learning / Q000502:physiology; D002940:Circadian Rhythm / Q000235:genetics / Q000502:physiology; D004195:Disease Models, Animal; D005106:Exploratory Behavior / Q000502:physiology; D005239:Fear / Q000502:physiology; D051860:Fragile X Messenger Ribonucleoprotein 1 / Q000235:genetics / Q000378:metabolism*; D005600:Fragile X Syndrome / Q000235:genetics* / Q000503:physiopathology*; D007859:Learning Disabilities / Q000209:etiology / Q000235:genetics; D008297:Male; D018782:Maze Learning / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009043:Motor Activity / Q000235:genetics*; D010641:Phenotype; D012919:Social Behavior
D051860:Fragile X Messenger Ribonucleoprotein 1; C497684:Fmr1 protein, mouse
activity; anxiety; circadian phase; fragile X; learning and memory; social behavior