huMECP2-R294X Mouse

Rett syndrome (RTT) is a severe X-linked neurodevelopmental disorder that primarily affects females and is one of the most common causes of severe intellectual disability in females ^[1]. The disorder is primarily caused by mutations in the MECP2 gene on the X chromosome. MECP2 encodes methyl-CpG-binding protein 2 (MeCP2), an important epigenetic regulator that participates in transcriptional regulation by recognizing methylated DNA and contributes to the maintenance of chromatin structure, playing important roles in neuronal development, synaptic function, and gene expression homeostasis ^[2-3]. Among these mutations, the p.R294X nonsense mutation can impair MeCP2 protein function and is one of the common pathogenic mutations associated with Rett syndrome, with close associations with various neurological abnormalities.

The huMECP2-R294X mouse model was generated by introducing the p.R294X point mutation into exon 4 of the humanized MECP2 gene using gene-editing technology. Its applications mainly include the investigation of the mechanisms underlying Rett syndrome (RTT) and the exploration of novel therapeutic strategies, such as gene therapy and antisense oligonucleotide (ASO)-based interventions. This model can provide a preclinical platform for evaluating the potential effects of various therapeutic approaches targeting the MECP2 pathway on neurological function.