Gene expression patterns in cMyBP-C?C10mut HCM mice and cMyBP-C(t/t) DCM mice

A 25-base pair deletion in the cardiac myosin binding protein-C (cMyBP-C) gene (MYBPC3), proposed to skip exon 33, modifies the C10 domain (cMyBP-C?C10mut) and is associated with hypertrophic cardiomyopathy (HCM) and heart failure, affecting approximately 100 million South Asians. However, the molecular mechanisms underlying the pathogenicity of cMyBP-C?C10mut in vivo are unknown. To determine whether expression of cMyBP-C?C10mut is sufficient to cause HCM and contractile dysfunction in vivo, we generated transgenic (TG) mice having cardiac-specific protein expression of cMyBP-C?C10mut at approximately half the level of endogenous cMyBP-C. At 12 weeks of age, significant hypertrophy was observed in TG mice expressing cMyBP-C?C10mut. Also RNA Sequencing revealed that genes related to muscle contraction and proteosome biological process are dysregulated. Similarly,to determine whether myocardial inflammation is associated with cardiac dysfunction in dilated cardiomyopathy (DCM) caused by MYBPC3 mutation, we used the well-characterized cMyBP-C(t/t) mouse model of DCM at 3months of age.RNA-seq analysis revealed the upregulation of inflammatory pathways in the DCM hearts. Overall design: The study included two mice models and its respective control. 1. cMyBP-C?C10mut mice (SS2)and non transgenic mice(SS1). 2. cMyBP-C(t/t) (SS5) and control mice (SS4)