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Heart RNA-seq of therapeutic RBM20 antisense oligonucleotide (ASO) treatment in a mouse model of heart failure with preserved ejection fraction (HFpEF)

ABSTRACT: We report the heart RNA-sequencing of control animals and animals of a mouse model of heart failure treated or not with RBM20 antisense oligonucleotide. This study aims to investigate the therapeutic effect of antisense oligonucleotide (ASO)-mediated downregulation of the cardiac splice factor RBM20 in a mouse model of heart failure with preserved ejection fraction. 8-week old wild type and titin N2B KO mice with increased wall stiffness were subcutaneously injected with 50 mg/kg/week RBM20 ASO for 8 weeks. RNA from 4 left ventricles per group were isolated using TRIzol followed by a clean-up with the QIAGEN RNA micro kit. The cDNA libraries were generated using the Illumina TruSeq Stranded mRNA LT Sample Prep Kit and 2x150 paired end sequenced on HiSeq4000. The RNA-Sequencing analysis confirms that RBM20 ASO treatment increased the expression of compliant titin isoforms and improved impaired ventricular filling and cardiac function. RNA-seq confirmed RBM20 dependent isoform changes of known targets such as Titin, Ldb3, Camk2d, and Ank3, and served as a sensitive indicator of potential side effects, largely limited to genes related to the immune response.

INSTRUMENT(S): Illumina HiSeq 4000

ORGANISM(S): Mus musculus

SUBMITTER: Thiago Britto Borges

PROVIDER: E-MTAB-9361 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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