Jamet, Sophie;
Ha, Seungshin;
Ho, Tzu-Hua;
Houghtaling, Scott;
Timms, Andrew;
Yu, Kai;
Paquette, Alison;
... Beier, David R; + view all
(2022)
The Arginine Methyltransferase Carm1 is Necessary for Heart Development.
G3: Genes | Genomes | Genetics
, Article jkac155. 10.1093/g3journal/jkac155.
(In press).
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Abstract
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 micro-computed tomography (micro-CT) imaging shows a range of cardiac defects. Most notably, many affected mid-gestation 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 (VSDs), Double Outlet Right Ventricle (DORV), and Persistent Truncus Arteriosus (PTA). 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 mis-localization 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.
| Type: | Article |
|---|---|
| Title: | The Arginine Methyltransferase Carm1 is Necessary for Heart Development |
| Location: | England |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1093/g3journal/jkac155 |
| Publisher version: | https://doi.org/10.1093/g3journal/jkac155 |
| Language: | English |
| Additional information: | VC The Author(s) 2022. Published by Oxford University Press on behalf of Genetics Society of America. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited. |
| Keywords: | ENU mutagenesis, Carm1, heart development, Pax3 |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health > Developmental Biology and Cancer Dept UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10152036 |
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