• Background: MYBPC3 is a gene encoding myosin-binding protein C, a crucial protein in the sarcomere. In hypertrophic cardiomyopathy (HCM), mutations in MYBPC3 are one of the most common genetic causes. These mutations can lead to abnormal sarcomere structure and function, causing myocardial hypertrophy and impaired relaxation. This disrupts the normal contraction and relaxation cycle of the heart, contributing to the symptoms and progression of HCM.
• Targeting strategy: The exons 3~28 of mouse Mybpc3 gene were knocked out in B-Mybpc3 KO mice.
• Validation: Mouse Mybpc3 mRNA was only detectable in wild-type C57BL/6JNifdc mice, but not in B-Mybpc3 KO mice. H&E-staining showed cardiac enlargement, ventricular wall thickening, and ventricular dilatation in homozygous B-Mybpc3 KO mice but not in wild-type mice, and the pathological changes in heart tissue is consistent with the characteristics of hypertrophic cardiomyopathy.
• Application: B-Mybpc3 KO mice is a disease model mouse of hypertrophic cardiomyopathy, which can be used for mechanism research of hypertrophic cardiomyopathy and drug efficacy research

Gene targeting strategy for B-Mybpc3 KO mice. The exons 3~28 of mouse Mybpc3 gene were knocked out in B-Mybpc3 KO mice.

mMybpc3 mRNA expression analysis in wild-type C57BL/6JNifdc mice and homozygous B-Mybpc3 KO mice by RT-PCR. Heart RNA were isolated from wild-type C57BL/6JNifdc mice (+/+) and homozygous B-Mybpc3 KO mice (-/-), then cDNA libraries were synthesized by reverse transcription, followed by PCR with mouse Mybpc3 primers. Mouse Mybpc3 mRNA was only detectable in wild-type mice but not in homozygous B-Mybpc3 KO mice.

Size Comparison of Heart Tissues. Heart tissue was collected from wild-type C57BL/6JNifdc mice (male, 7-week-old, n=3) and homozygous B-Mybpc3 KO mice (male, 7-week-old, n=3). Heart from homozygous B-Mybpc3 KO mice is larger than that of wild-type mice.

Histopathological analysis of heart tissue in homozygous B-Mybpc3 KO mice. Heart was collected from wild-type C57BL/6JNifdc mice (+/+) (male, 7-week-old, n=2) and homozygous B-Mybpc3 KO mice (-/-) (male, 7-week-old, n=2) and H&E-staining were performed. (A) Longitudinal section. (B) Transverse section of the heart. Results showed cardiac enlargement, ventricular wall thickening, and ventricular dilatation in homozygous B-Mybpc3 KO mice but not in wild-type mice, and the pathological changes in heart tissue is consistent with the characteristics of hypertrophic cardiomyopathy.