Fragile X syndrome (FXS) is an intellectual disability attributable to loss of fragile X protein (FMRP). We previously demonstrated that FMRP binds mRNAs targeted for nonsense-mediated mRNA decay (NMD) and that FMRP loss results in hyperactivated NMD and inhibition of neuronal differentiation in human stem cells. We show here that NMD is hyperactivated during the development of the cerebral cortex, hippocampus, and cerebellum in the Fmr1-knockout (KO) mouse during embryonic and early postnatal periods. Our findings demonstrate that NMD regulates many neuronal mRNAs that are important for mouse brain development. We reveal the abnormal regulation of these mRNAs in the Fmr1-KO mouse, a model of FXS, and highlight the importance of early intervention.

中文翻译：

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Fmr1 敲除小鼠脆性 X 综合征模型大脑发育过程中 NMD 异常


脆性 X 综合征 (FXS) 是一种由于脆性 X 蛋白 (FMRP) 缺失而导致的智力障碍。我们之前证明，FMRP 结合针对无义介导的 mRNA 衰减 (NMD) 的 mRNA，并且 FMRP 丢失会导致 NMD 过度激活并抑制人类干细胞中的神经元分化。我们在此表明​​，Fmr1 敲除 (KO) 小鼠在胚胎期和产后早期的大脑皮层、海马和小脑发育过程中 NMD 过度激活。我们的研究结果表明，NMD 调节许多对小鼠大脑发育很重要的神经元 mRNA。我们揭示了 Fmr1-KO 小鼠（FXS 模型）中这些 mRNA 的异常调节，并强调了早期干预的重要性。