Saré Rachel Michelle, Figueroa Christopher, Lemons Abigail, Loutaev Inna, Beebe Smith Carolyn
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.
Brain Sci. 2019 Jan 16;9(1):13. doi: 10.3390/brainsci9010013.
Fragile X syndrome (FXS) is caused by silencing of the 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 display similar behavioral abnormalities as knockout (KO) mice. In this study, we expand upon the behavioral phenotypes of KO and (Het) mice and compare them with KO/ Het mice. We find that KO and KO/ Het mice are similarly hyperactive compared to WT and Het mice. KO/ Het mice have more severe learning and memory impairments than KO mice. KO mice display significantly impaired social behaviors compared to WT mice, which are paradoxically reversed in KO/ Het mice. These results highlight the important functional consequences of loss or reduction of FMRP and FXR2P.
脆性X综合征（FXS）是由该基因沉默导致脆性X智力低下蛋白（FMRP）产物缺失引起的。FXS是智力残疾最常见的单基因病因。已知FMRP有两种哺乳动物旁系同源物，即FXR1P和FXR2P。FXR1P和FXR2P的功能及其在产生或调节FXS中观察到的表型方面可能发挥的作用尚待确定。先前的研究表明，缺乏该基因的小鼠表现出与该基因敲除（KO）小鼠相似的行为异常。在本研究中，我们扩展了该基因敲除（KO）和杂合（Het）小鼠的行为表型，并将它们与该基因敲除/杂合（KO/Het）小鼠进行比较。我们发现，与野生型（WT）和杂合小鼠相比，该基因敲除（KO）和该基因敲除/杂合（KO/Het）小鼠同样多动。该基因敲除/杂合（KO/Het）小鼠比该基因敲除（KO）小鼠有更严重的学习和记忆障碍。与野生型小鼠相比，该基因敲除（KO）小鼠表现出明显受损的社交行为，而在该基因敲除/杂合（KO/Het）小鼠中这种行为却出现了相反的变化。这些结果突出了FMRP和FXR2P缺失或减少的重要功能后果。
