Mecp2 KO Mouse

Rett syndrome (RTT) is a rare progressive neurodevelopmental disorder primarily caused by loss-of-function (LOF) mutations in the MECP2 gene located on the X chromosome. This condition predominantly affects females, with an incidence of approximately 1 in 10,000 live female births ^[1]. RTT symptoms typically manifest during early childhood and include developmental delay, loss of speech, stereotypic hand movements, abnormal muscle tone, and respiratory problems. Currently, the only approved treatment for RTT is trofinetide, which can alleviate symptoms to some extent; however, its high cost and inability to cure the disease remain significant challenges ^[2]. The MECP2 gene encodes an epigenetic regulator critical for normal development and function of the nervous system. The MeCP2 protein is highly expressed in neurons, where it binds to methylated DNA to repress transcription and regulate processes such as gene expression, chromatin architecture, RNA splicing, and microRNA processing ^[3]. Loss of MeCP2 disrupts post-transcriptional modification of numerous genes, leading to structural and functional abnormalities in neurons and synapses, including disrupted synaptic connections and altered neurotransmitter systems, ultimately resulting in characteristic RTT phenotypes.

This strain is a Mecp2 gene knockout (KO) mouse model of Rett syndrome generated by disrupting the Mecp2 gene (the murine ortholog of the human MECP2 gene) on the X chromosome using genome-editing techniques. Studies have demonstrated that Mecp2 KO mice exhibit phenotypes closely resembling those of human RTT, including shortened lifespan, motor impairments, abnormal breathing, stereotypic behaviors, anxiety, social interaction deficits, and cognitive impairments ^[4]. These features make the Mecp2 KO mouse a valuable tool for studying the pathogenesis of RTT, drug screening, and the development of gene therapies in preclinical research. Preliminary validation data indicate that this strain exhibits abnormalities in body weight and survival rates, along with progressive RTT phenotypes such as gait defects, hindlimb clasping, tremors, motor dysfunction, and respiratory abnormalities.