Heart RNA-Seq of cardiomyocyte-specific and inducible Prmt5 knockout mouse model
Our study introduces a novel animal model featuring a cardiomyocyte-specific, inducible knockout of the Prmt5. The primary aim of this model is to investigate the regulatory mechanisms of PRMT5, the main representative of type II PRMTs. We found that PRMT5 controls Acadvl mRNA splicing and that disruptions in this regulation lead to loss of functional ACADVL and cardiac dysfunction. Importantly, we also show that maintained expression of ACADVL is cardioprotective highlighting a potential therapeutic strategy.   The animal model was created using a conditional-ready allele of Prmt5 sourced from the European Mouse Mutant Archive (EMMA, specifically the B6Brd;B6N-Tyrc-Brd Atm1Brd Prmt5tm2a(EUCOMM)WtsiPrmt5 strain). To achieve a conditional knockout, the lacZ reporter was excised using flippase recombinase. The resulting Prmt5loxP/loxP mice were then bred with transgenic mice expressing an inducible Cre recombinase under the control of the alpha-myosin heavy chain promoter (alpha-MHC-MerCreMer), enabling deletion of Prmt5 in cardiomyocytes.   We provide RNA-sequencing raw and aligned files for two datasets. The first dataset comprises Ctrl. and cKO left-ventricular cardiac tissue upon treatment with either saline (control) or isoprenaline (ISO). The second dataset comprises isolated cardiomyocyte-specific nuclei of Ctrl. and cKO animals.  The model enables a controlled study of PRMT5-intrinsic role in heart pathophysiology, with translational relevance for heart failure. Our methodology, including genetic manipulation and the observation of phenotypic outcomes, paves the way for further exploration into the metabolic underpinnings of cardiac health.  The animal model was created using a conditional-ready allele of Prmt5 sourced from the European Mouse Mutant Archive (EMMA, specifically the B6Brd;B6N-Tyrc-Brd Atm1Brd Prmt5tm2a(EUCOMM)WtsiPrmt5 strain). To achieve a conditional knockout, the lacZ reporter was excised using flippase recombinase. The resulting Prmt5loxP/loxP mice were then bred with transgenic mice expressing an inducible Cre recombinase under the control of the alpha-myosin heavy chain promoter (alpha-MHC-MerCreMer), enabling deletion of Prmt5 in cardiomyocytes.   We provide RNA-sequencing raw and aligned files for two datasets. The first dataset comprises WT and cKO for treated with either saline (control) or isoprenaline. The second dataset comprises WT and cKO of nuclear fractions of isolated cardiomyocytes.  The model enables a controlled study of Prmt5's role in heart physiology and pathology, with the potential to unlock new interventions for heart failure. Our methodology, including genetic manipulation and the observation of phenotypic outcomes, paves the way for further exploration into the metabolic underpinnings of cardiac health.
Our study introduces a novel animal model featuring a cardiomyocyte-specific, inducible knockout of the Prmt5. The primary aim of this model is to investigate the regulatory mechanisms of PRMT5, the main representative of type II PRMTs. We found that PRMT5 controls Acadvl mRNA splicing and that disruptions in this regulation lead to loss of functional ACADVL and cardiac dysfunction. Importantly, we also show that maintained expression of ACADVL is cardioprotective highlighting a potential therapeutic strategy.   The animal model was created using a conditional-ready allele of Prmt5 sourced from the European Mouse Mutant Archive (EMMA, specifically the B6Brd;B6N-Tyrc-Brd Atm1Brd Prmt5tm2a(EUCOMM)WtsiPrmt5 strain). To achieve a conditional knockout, the lacZ reporter was excised using flippase recombinase. The resulting Prmt5loxP/loxP mice were then bred with transgenic mice expressing an inducible Cre recombinase under the control of the alpha-myosin heavy chain promoter (alpha-MHC-MerCreMer), enabling deletion of Prmt5 in cardiomyocytes.   We provide RNA-sequencing raw and aligned files for two datasets. The first dataset comprises Ctrl. and cKO left-ventricular cardiac tissue upon treatment with either saline (control) or isoprenaline (ISO). The second dataset comprises isolated cardiomyocyte-specific nuclei of Ctrl. and cKO animals.  The model enables a controlled study of PRMT5-intrinsic role in heart pathophysiology, with translational relevance for heart failure. Our methodology, including genetic manipulation and the observation of phenotypic outcomes, paves the way for further exploration into the metabolic underpinnings of cardiac health.  The animal model was created using a conditional-ready allele of Prmt5 sourced from the European Mouse Mutant Archive (EMMA, specifically the B6Brd;B6N-Tyrc-Brd Atm1Brd Prmt5tm2a(EUCOMM)WtsiPrmt5 strain). To achieve a conditional knockout, the lacZ reporter was excised using flippase recombinase. The resulting Prmt5loxP/loxP mice were then bred with transgenic mice expressing an inducible Cre recombinase under the control of the alpha-myosin heavy chain promoter (alpha-MHC-MerCreMer), enabling deletion of Prmt5 in cardiomyocytes.   We provide RNA-sequencing raw and aligned files for two datasets. The first dataset comprises WT and cKO for treated with either saline (control) or isoprenaline. The second dataset comprises WT and cKO of nuclear fractions of isolated cardiomyocytes.  The model enables a controlled study of Prmt5's role in heart physiology and pathology, with the potential to unlock new interventions for heart failure. Our methodology, including genetic manipulation and the observation of phenotypic outcomes, paves the way for further exploration into the metabolic underpinnings of cardiac health.
European Bioinformatics Institute