Congenital heart defects (CHD) are the most common congenital malformations in newborns and are a major cause of infant morbidity and mortality. Despite many genetic studies, much of the genetic mechanisms behind normal and abnormal heart development remain to be elucidated.
The Myomesin 2 gene ( MYOM2) encodes a protein located in the M-band of the sarcomere in cardiac and skeletal muscle. A potential role for MYOM2 in the assembly of sarcomeric Titin has been proposed. The assembly of the sarcomere is of tremendous importance for a fully functional skeletal and cardiac muscle and mutations in sarcomere genes like ACTC1, MYH6 and MYH7 have previously been associated with CHD and rare MYOM2 variants have been reported in CHD patients. This study focuses on the role of MYOM2 during heart development. The zebrafish genome encodes a myom2 gene with a 55% homology to the hyman MYOM2. Therefore the zebrafish was used to model the expression of myom2 during development and to explore the role of gene knockdown in live developing zebrafish hearts.
In situ hybridization showed that myom2 is expressed specifically in heart and skeletal muscle during zebrafish embryonic development. We also found myom2 to be duplicated, with similar expression patterns. Two approaches to knock down the gene in zebrafish were used. First zebrafish carrying a nonsense mutation in the myom2a gene was obtained from the Zebrafish Mutation Project (Sanger Institute, UK). No obvious cardiac or muscle phenotype was present in homozygous mutants, suggesting that mutants compensate for the loss of myom2 function. Whereas the development of zebrafish embryos injected with morpholinos targeting myom2awas delayed and developmental defects were observed. Targeting myom2b with morpholinos did not differ from control injected wild type embryos. Interestingly the myom2b morpholino did show developmental changes in myom2a mutants.
The preliminary data indicates a possible role of myom2 in heart development, but further experiments are needed.