B6-hDMD (E49-53)*Del E50 Mouse

Duchenne Muscular Dystrophy (DMD) is a severe, progressive, and disabling X-linked recessive genetic disorder characterized primarily by muscle atrophy. This disease leads to motor impairments, eventually requiring assisted ventilation, and often results in premature death. The primary cause of DMD is mutations in the DMD gene, which encodes the dystrophin protein. These mutations lead to a reduction or absence of dystrophin in muscle tissue, resulting in muscle atrophy and related complications ^[1]. The lack of dystrophin leads to the breakdown of the dystrophin-associated protein complex (DAPC) within the muscle membrane, disrupting the interaction between actin and the extracellular matrix, making the muscles more susceptible to damage. This susceptibility results in the gradual loss of muscle tissue and function, potentially leading to cardiomyopathy ^[2]. Researchers have identified thousands of different DMD gene mutations in patients with DMD. Deletion mutations account for approximately 60%–70%, while duplication mutations account for 5%–15%. These mutations are primarily concentrated in hotspot regions of the DMD gene, specifically between exons 45-55 (47%) and exons 3-9 (7%) ^[1].

Currently, gene therapy approaches for Duchenne Muscular Dystrophy (DMD) primarily include exon skipping and AAV supplementation, as well as emerging gene editing techniques like CRISPR. The exon skipping strategy involves using antisense oligonucleotide (ASO) drugs to bind to specific sequences of pre-mRNA, skipping the mutated exon and restoring the open reading frame (ORF) integrity, thus producing a truncated but partially functional dystrophin protein. Several ASO drugs targeting the DMD gene have been approved, such as Eteplirsen (targeting exon 51), Golodirsen (targeting exon 53), and Casimersen (targeting exon 45) developed by Sarepta, and Viltolarsen (targeting exon 53) developed by Nippon Shinyaku. Since most ASO and CRISPR-based gene editing therapies target the human DMD gene, humanizing mouse genes helps accelerate clinical applications for DMD therapies, considering the genetic differences between animals and humans.

The B6-hDMD (E49-53)*Del E50 mouse is a humanized model of the Dmd gene, in which the genomic sequences corresponding to exons 49–53 and their flanking regions in the mouse Dmd gene have been replaced with the corresponding human DMD gene sequences, followed by knock-out of exon 50 in the human DMD gene within the mouse genome. This model is suitable for research on Duchenne muscular dystrophy. In addition, based on the independently developed TurboKnockout fusion BAC recombination technology, Cyagen provides other humanized models such as [hE49-53], [hE44-45, c.6438+2 T to A], [hE8-30], covering most popular research areas and offering customized services based on different mutation needs.