Comparative Behavioral Phenotypes of Fmr1 KO, Fxr2 Het, and Fmr1 KO/ Fxr2 Het Mice

Rachel Michelle Saré; Christopher Figueroa; Abigail Lemons; Inna Loutaev; Carolyn Beebe Smith

doi:10.3390/brainsci9010013

Comparative Behavioral Phenotypes of Fmr1 KO, Fxr2 Het, and Fmr1 KO/ Fxr2 Het Mice

Brain Sci. 2019 Jan 16;9(1):13. doi: 10.3390/brainsci9010013.

Authors

Rachel Michelle Saré¹, Christopher Figueroa², Abigail Lemons³, Inna Loutaev⁴, Carolyn Beebe Smith⁵

Affiliations

¹ Section on Neuroadaptation and Protein Metabolism, National Institute of Mental Health, National Institutes of Health, Department of Health and Human Services, Bethesda, MD 20814, USA. Rachel.Sare@nih.gov.
² Section on Neuroadaptation and Protein Metabolism, National Institute of Mental Health, National Institutes of Health, Department of Health and Human Services, Bethesda, MD 20814, USA. Christopher.Figueroa@nih.gov.
³ Section on Neuroadaptation and Protein Metabolism, National Institute of Mental Health, National Institutes of Health, Department of Health and Human Services, Bethesda, MD 20814, USA. Abigail.Lemons@nih.gov.
⁴ Section on Neuroadaptation and Protein Metabolism, National Institute of Mental Health, National Institutes of Health, Department of Health and Human Services, Bethesda, MD 20814, USA. Loutaev.inna@nih.gov.
⁵ Section on Neuroadaptation and Protein Metabolism, National Institute of Mental Health, National Institutes of Health, Department of Health and Human Services, Bethesda, MD 20814, USA. beebe@mail.nih.gov.

Abstract

Fragile X syndrome (FXS) is caused by silencing of the FMR1 gene leading to loss of the protein product fragile X mental retardation protein (FMRP). FXS is the most common monogenic cause of intellectual disability. There are two known mammalian paralogs of FMRP, FXR1P, and FXR2P. The functions of FXR1P and FXR2P and their possible roles in producing or modulating the phenotype observed in FXS are yet to be identified. Previous studies have revealed that mice lacking Fxr2 display similar behavioral abnormalities as Fmr1 knockout (KO) mice. In this study, we expand upon the behavioral phenotypes of Fmr1 KO and Fxr2^+/- (Het) mice and compare them with Fmr1 KO/Fxr2 Het mice. We find that Fmr1 KO and Fmr1 KO/Fxr2 Het mice are similarly hyperactive compared to WT and Fxr2 Het mice. Fmr1 KO/Fxr2 Het mice have more severe learning and memory impairments than Fmr1 KO mice. Fmr1 KO mice display significantly impaired social behaviors compared to WT mice, which are paradoxically reversed in Fmr1 KO/Fxr2 Het mice. These results highlight the important functional consequences of loss or reduction of FMRP and FXR2P.

Keywords: FMRP; Fmr1; Fragile X; Fxr2.

Abstract

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