Knockout mouse model for Fxr2: a model for mental retardation
- PMID: 11875043
- DOI: 10.1093/hmg/11.5.487
Knockout mouse model for Fxr2: a model for mental retardation
Abstract
Fragile X syndrome is a common form of mental retardation caused by the absence of the FMR1 protein, FMRP. Fmr1 knockout mice exhibit a phenotype with some similarities to humans, such as macro-orchidism and behavioral abnormalities. Two homologs of FMRP have been identified, FXR1P and FXR2P. These proteins show high sequence similarity, including all functional domains identified in FMRP, such as RNA binding domains. They have an overlap in tissue distribution to that of FMRP. Interactions between the three FXR proteins have also been described. FXR2P shows high expression in brain and testis, like FMRP. To study the function of FXR2P, we generated an Fxr2 knockout mouse model. No pathological differences between knockout and wild-type mice were found in brain or testis. Given the behavioral phenotype in fragile X patients and the phenotype previously reported for the Fmr1 knockout mouse, we performed a thorough evaluation of the Fxr2 knockout phenotype using a behavioral test battery. Fxr2 knockout mice were hyperactive (i.e. traveled a greater distance, spent more time moving and moved faster) in the open-field test, impaired on the rotarod test, had reduced levels of prepulse inhibition, displayed less contextual conditioned fear, impaired at locating the hidden platform in the Morris water task and were less sensitive to a heat stimulus. Interestingly, there are some behavioral phenotypes in Fxr2 knockout mice which are similar to those observed in Fmr1 knockout mice, but there are also some different behavioral abnormalities that are only observed in the Fxr2 mutant mice. The findings implicate a role for Fxr2 in central nervous system function.
Similar articles
-
Exaggerated behavioral phenotypes in Fmr1/Fxr2 double knockout mice reveal a functional genetic interaction between Fragile X-related proteins.Hum Mol Genet. 2006 Jun 15;15(12):1984-94. doi: 10.1093/hmg/ddl121. Epub 2006 May 4. Hum Mol Genet. 2006. PMID: 16675531
-
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. Brain Sci. 2019. PMID: 30654445 Free PMC article.
-
Altered hippocampal synaptic plasticity in the FMR1 gene family knockout mouse models.J Neurophysiol. 2009 May;101(5):2572-80. doi: 10.1152/jn.90558.2008. Epub 2009 Feb 25. J Neurophysiol. 2009. PMID: 19244359 Free PMC article.
-
Restoring the phenotype of fragile X syndrome: insight from the mouse model.Curr Mol Med. 2001 Sep;1(4):447-55. doi: 10.2174/1566524013363492. Curr Mol Med. 2001. PMID: 11899089 Review.
-
Biology of the fragile X mental retardation protein, an RNA-binding protein.Biochem Cell Biol. 1999;77(4):331-42. Biochem Cell Biol. 1999. PMID: 10546896 Review.
Cited by
-
FMRP-mediated spatial regulation of physiologic NMD targets in neuronal cells.Genome Biol. 2024 Jan 23;25(1):31. doi: 10.1186/s13059-023-03146-x. Genome Biol. 2024. PMID: 38263082 Free PMC article. Review.
-
ILF3 prion-like domain regulates gene expression and fear memory under chronic stress.iScience. 2023 Feb 19;26(3):106229. doi: 10.1016/j.isci.2023.106229. eCollection 2023 Mar 17. iScience. 2023. PMID: 36876121 Free PMC article.
-
Abnormal sensory perception masks behavioral performance of Grin1 knockdown mice.Genes Brain Behav. 2022 Jul;21(6):e12825. doi: 10.1111/gbb.12825. Epub 2022 Jun 15. Genes Brain Behav. 2022. PMID: 35705513 Free PMC article.
-
Holocarboxylase synthetase knockout is embryonic lethal in mice.PLoS One. 2022 Apr 6;17(4):e0265539. doi: 10.1371/journal.pone.0265539. eCollection 2022. PLoS One. 2022. PMID: 35385533 Free PMC article.
-
Absence of RNA-binding protein FXR2P prevents prolonged phase of kainate-induced seizures.EMBO Rep. 2021 Apr 7;22(4):e51404. doi: 10.15252/embr.202051404. Epub 2021 Mar 28. EMBO Rep. 2021. PMID: 33779029 Free PMC article.
Publication types
MeSH terms
Substances
Grants and funding
LinkOut - more resources
Full Text Sources
Other Literature Sources
Molecular Biology Databases
Research Materials