Bulk RNA-sequencing from whole heart lysates of a mouse model of hypertrophic cardiomyopathy after TTL overexpression.

Reducing microtubule detyrosination has been shown to inprove contractility in heart failure cardiomyocytes. To evaluate the feasibility of targeting the detyrosinated microtubule network for treatment of cardiomyopathy in an in-vivo context we overexpressed tubulin tyrosine ligase (TTL) by AAV9 delivery in a mouse model of HCM (Mybpc3-/-) and an empty vector as control in HCM and WT mice. Overall design: We overexpressed AAV9-TTL or AAV9-empty in p21 mice (2.25E11 vg/g) and monitored heart function for 12 weeks by echocardiography. Animals were then subjected to hemodynamic measurements and sacrificed, before heart tissue was harvested, snap frozen and powdered. RNA was extracted with the Promega SV total RNA kit. n=3 animals were included for RNAseq.