The arginine methyltransferase Carm1 is necessary for heart development.

Autor: Jamet S; Center for Developmental Biology and Regenerative Medicine, Seattle Children's Research Institute, Seattle, WA 98101, USA., Ha S; Center for Developmental Biology and Regenerative Medicine, Seattle Children's Research Institute, Seattle, WA 98101, USA., Ho TH; Center for Developmental Biology and Regenerative Medicine, Seattle Children's Research Institute, Seattle, WA 98101, USA., Houghtaling S; Center for Developmental Biology and Regenerative Medicine, Seattle Children's Research Institute, Seattle, WA 98101, USA., Timms A; Center for Developmental Biology and Regenerative Medicine, Seattle Children's Research Institute, Seattle, WA 98101, USA., Yu K; Center for Developmental Biology and Regenerative Medicine, Seattle Children's Research Institute, Seattle, WA 98101, USA.; Department of Pediatrics, University of Washington School of Medicine, Seattle, WA 98195, USA., Paquette A; Center for Developmental Biology and Regenerative Medicine, Seattle Children's Research Institute, Seattle, WA 98101, USA.; Department of Pediatrics, University of Washington School of Medicine, Seattle, WA 98195, USA., Maga AM; Center for Developmental Biology and Regenerative Medicine, Seattle Children's Research Institute, Seattle, WA 98101, USA.; Department of Pediatrics, University of Washington School of Medicine, Seattle, WA 98195, USA., Greene NDE; Developmental Biology & Cancer Department, UCL Great Ormond Street Institute of Child Health, London WC1N 1EH, UK., Beier DR; Center for Developmental Biology and Regenerative Medicine, Seattle Children's Research Institute, Seattle, WA 98101, USA.; Department of Pediatrics, University of Washington School of Medicine, Seattle, WA 98195, USA.
Jazyk: angličtina
Zdroj: G3 (Bethesda, Md.) [G3 (Bethesda)] 2022 Jul 29; Vol. 12 (8).
DOI: 10.1093/g3journal/jkac155
Abstrakt: To discover genes implicated in human congenital disorders, we performed ENU mutagenesis in the mouse and screened for mutations affecting embryonic development. In this work, we report defects of heart development in mice homozygous for a mutation of coactivator-associated arginine methyltransferase 1 (Carm1). While Carm1 has been extensively studied, it has never been previously associated with a role in heart development. Phenotype analysis combining histology and microcomputed tomography imaging shows a range of cardiac defects. Most notably, many affected midgestation embryos appear to have cardiac rupture and hemorrhaging in the thorax. Mice that survive to late gestation show a variety of cardiac defects, including ventricular septal defects, double outlet right ventricle, and persistent truncus arteriosus. Transcriptome analyses of the mutant embryos by mRNA-seq reveal the perturbation of several genes involved in cardiac morphogenesis and muscle development and function. In addition, we observe the mislocalization of cardiac neural crest cells at E12.5 in the outflow tract. The cardiac phenotype of Carm1 mutant embryos is similar to that of Pax3 null mutants, and PAX3 is a putative target of CARM1. However, our analysis does not support the hypothesis that developmental defects in Carm1 mutant embryos are primarily due to a functional defect of PAX3.
(© The Author(s) 2022. Published by Oxford University Press on behalf of Genetics Society of America.)
Databáze: MEDLINE
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