Comparative Behavioral Phenotypes of Fmr1 KO, Fxr2 Het, and Fmr1 KO/Fxr2 Het Mice
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 F...
| Main Authors: | , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2019-01-01
|
| Series: | Brain Sciences |
| Subjects: | |
| Online Access: | http://www.mdpi.com/2076-3425/9/1/13 |
| _version_ | 1811221320167325696 |
|---|---|
| author | Rachel Michelle Saré Christopher Figueroa Abigail Lemons Inna Loutaev Carolyn Beebe Smith |
| author_facet | Rachel Michelle Saré Christopher Figueroa Abigail Lemons Inna Loutaev Carolyn Beebe Smith |
| author_sort | Rachel Michelle Saré |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-12T07:58:30Z |
| format | Article |
| id | doaj.art-3742287e08b74c718e2ab0adb3563d6e |
| institution | Directory Open Access Journal |
| issn | 2076-3425 |
| language | English |
| last_indexed | 2024-04-12T07:58:30Z |
| publishDate | 2019-01-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Brain Sciences |
| spelling | doaj.art-3742287e08b74c718e2ab0adb3563d6e2022-12-22T03:41:25ZengMDPI AGBrain Sciences2076-34252019-01-01911310.3390/brainsci9010013brainsci9010013Comparative Behavioral Phenotypes of Fmr1 KO, Fxr2 Het, and Fmr1 KO/Fxr2 Het MiceRachel Michelle Saré0Christopher Figueroa1Abigail Lemons2Inna Loutaev3Carolyn Beebe Smith4Section on Neuroadaptation and Protein Metabolism, National Institute of Mental Health, National Institutes of Health, Department of Health and Human Services, Bethesda, MD 20814, USASection on Neuroadaptation and Protein Metabolism, National Institute of Mental Health, National Institutes of Health, Department of Health and Human Services, Bethesda, MD 20814, USASection on Neuroadaptation and Protein Metabolism, National Institute of Mental Health, National Institutes of Health, Department of Health and Human Services, Bethesda, MD 20814, USASection on Neuroadaptation and Protein Metabolism, National Institute of Mental Health, National Institutes of Health, Department of Health and Human Services, Bethesda, MD 20814, USASection on Neuroadaptation and Protein Metabolism, National Institute of Mental Health, National Institutes of Health, Department of Health and Human Services, Bethesda, MD 20814, USAFragile 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.http://www.mdpi.com/2076-3425/9/1/13Fragile XFMRPFxr2Fmr1 |
| spellingShingle | Rachel Michelle Saré Christopher Figueroa Abigail Lemons Inna Loutaev Carolyn Beebe Smith Comparative Behavioral Phenotypes of Fmr1 KO, Fxr2 Het, and Fmr1 KO/Fxr2 Het Mice Brain Sciences Fragile X FMRP Fxr2 Fmr1 |
| title | Comparative Behavioral Phenotypes of Fmr1 KO, Fxr2 Het, and Fmr1 KO/Fxr2 Het Mice |
| title_full | Comparative Behavioral Phenotypes of Fmr1 KO, Fxr2 Het, and Fmr1 KO/Fxr2 Het Mice |
| title_fullStr | Comparative Behavioral Phenotypes of Fmr1 KO, Fxr2 Het, and Fmr1 KO/Fxr2 Het Mice |
| title_full_unstemmed | Comparative Behavioral Phenotypes of Fmr1 KO, Fxr2 Het, and Fmr1 KO/Fxr2 Het Mice |
| title_short | Comparative Behavioral Phenotypes of Fmr1 KO, Fxr2 Het, and Fmr1 KO/Fxr2 Het Mice |
| title_sort | comparative behavioral phenotypes of fmr1 ko fxr2 het and fmr1 ko fxr2 het mice |
| topic | Fragile X FMRP Fxr2 Fmr1 |
| url | http://www.mdpi.com/2076-3425/9/1/13 |
| work_keys_str_mv | AT rachelmichellesare comparativebehavioralphenotypesoffmr1kofxr2hetandfmr1kofxr2hetmice AT christopherfigueroa comparativebehavioralphenotypesoffmr1kofxr2hetandfmr1kofxr2hetmice AT abigaillemons comparativebehavioralphenotypesoffmr1kofxr2hetandfmr1kofxr2hetmice AT innaloutaev comparativebehavioralphenotypesoffmr1kofxr2hetandfmr1kofxr2hetmice AT carolynbeebesmith comparativebehavioralphenotypesoffmr1kofxr2hetandfmr1kofxr2hetmice |