Rett syndrome (RTT) is an X-linked dominant neurodevelopmental disorder that occurs predominantly in female infants and young children. The incidence is approximately 1 in 10,000–15,000 females. Clinical features include intellectual disability, loss of language function, stereotyped hand movements, and gait abnormalities. Affected children typically have a period of normal development followed by stagnation of head circumference growth at 6–18 months of age, and regression of acquired skills. Overt cognitive and motor impairments develop 1–2 years later. Mutations in the methyl-CpG-binding protein 2 (MECP2) gene account for >90% of RTT cases. MECP2 is a nuclear protein that binds to methylated DNA to regulate gene transcription. MECP2 duplications cause MECP2 duplication syndrome (MDS), while functional deficiency of MECP2 impairs the production of this nuclear protein, leading to central nervous system functional maturation disorders that affect learning and memory functions, resulting in RTT.

Treatment for RTT focuses mainly on gene supplementation therapy based on adeno-associated virus (AAV) vectors. This involves delivering human MECP2 genes via AAV vectors to compensate for the deficiency of MECP2 genes in patients. However, the large size of the MECP2 gene exceeds the delivery capacity of most vectors, and over-expression of the MECP2 gene can also lead to serious neurological diseases. These limitations have hindered the development of this therapy. Therefore, DNA/RNA editing to repair MECP2 gene mutations and restore normal expression of MECP2 protein has received widespread attention. Currently, multiple research groups have used CRISPR-based gene editing technology to repair mutations in the MECP2 gene in induced pluripotent stem cells (iPSCs) or ex vivo patient cells ^[1-2]. Animal studies are an essential part of preclinical research. RTT therapies based on small nucleic acids, CRISPR gene editing technology, base editors, and RNA editing technology target the human MECP2 gene. Humanized mouse models can help advance gene therapy drug pipelines into clinical stages ^[3-4].

This strain is a humanized MECP2 gene mouse model that can be used for RTT research. Homozygous B6-hMECP2 mice are viable and fertile. Additionally, based on the independently developed TurboKnockout fusion BAC recombination technology, Cyagen can also generate hot mutation models based on this strain (B6-hMECP2*T158M, Catalog Number: C001569) and provide customized services for specific mutations to meet experimental needs in pharmacology and other RTT-related fields.