MYBPC3 (myosin-binding protein C3) is a cardiac sarcomere-associated protein encoded by the MYBPC3 gene and serves as a key structural and functional regulator of cardiac contraction ^[1]. In normal tissues, MYBPC3 is predominantly expressed in the heart, where it plays critical roles in cardiac muscle contraction, sarcomere assembly, and heart rate regulation. Dysfunction of this protein is closely associated with various cardiomyopathies. Mutations in MYBPC3 represent one of the most common genetic causes of familial hypertrophic cardiomyopathy (HCM), with the majority being truncating mutations that lead to haploinsufficiency. These mutations can result in cardiac hypertrophy, fibrosis, arrhythmias, heart failure, and an increased risk of sudden cardiac death ^[2-3]. In addition, MYBPC3 variants are also associated with dilated cardiomyopathy (DCM) and other forms of cardiomyopathy ^[4]. The huMYBPC3 mouse is a humanized model generated by replacing the sequence from the start codon to the 3'UTR in the murine Mybpc3 gene with the corresponding sequence of human MYBPC3. This model is suitable for evaluating the in vivo efficacy and safety of MYBPC3-targeted therapeutics, including gene therapies (such as AAV-mediated delivery), small-molecule drugs, and gene editing therapies. Furthermore, it is applicable to research on the pathogenesis of hypertrophic cardiomyopathy (HCM) and other MYBPC3-related cardiomyopathies, as well as studies on cardiac function, sarcomere structure, and combination therapy strategies.

Dock3 is located on chromosome 9 of mice. Nuclease Technology will be used to design sgRNA; Dock3 knockout mice will be obtained by applying high-throughput electroporation of fertilized eggs. After sexual maturity, sperm were collected for cryopreservation.