New genetic finding sheds light on congenital heart disease

New genetic finding sheds light for congenital heart disease
VGLL4 deletion resulted in perinatal lethality: (A) Vgll4 gene structure showing Vgll4-mutant allele. Green and red letters indicate wild-type and d46 mutant amino acid sequences, respectively; * indicates a premature stop codon; (B) distribution of genotypes at E16.5, E18.5, and P0. Embryo/pup numbers for each genotype are displayed in the bar graph. **, Mendelian ratio chi-squared test, p < 0.01; (C) survival curve of Vgll4 d46/+ (Vhet) and Vgll4 d46/d46 (Vko) pups. Postnatal day 0 (P0) was designated as the date of delivery. For each group, N = 12; (D) gross morphology of embryos and mouse pups at indicated ages. Scale bar: 5 mm; (E) body weight at E18.5; (F) mouse pups’ body weight gain in the first 5 days after delivery. N = 3; (G) gross morphology of mouse pups at P5; (H) cardiac Vgll4 mRNA expression. E13.5 hearts were collected for mRNA isolation and qRT-PCR measurement. TDU1 domain of Vgll4 was not detectable in the Vgll4 mutant transcripts. (E,H), Student’s t-test: **** p < 0.0001. N = 5–6. Credit: Cells (2022). DOI: 10.3390/cells11182832

A new study led by the Masonic Medical Research Institute published in the journal Cells shows for the first time that a particular gene, called VGLL4, is required for embryo development but is dispensable for myocardial growth. This fact was previously unknown, and with this discovery, medical researchers now have useful new information about heart cell development.

Congenital heart disease is one of the leading causes of pediatric morbidity and mortality, which is why it is important to decipher the molecular mechanisms that control heart development. Cardiovascular development has become a crucial element of understanding congenital heart diseases, and the more we know about this, the better we can treat heart malformations.

"Vestigial like family member 4" is a protein that is encoded by the VGLL4 gene; this is a transcriptional cofactor of VGLL family, found in many organs and tissues. VGLL4 has been pinpointed to be a , and it has been thoroughly researched in .

To understand the VGLL4 function in the heart, the authors generated two VGLL4 loss-of-function mouse lines: a germline VGLL4 depletion allele and a cardiomyocyte-specific VGLL4 depletion allele. The analysis of the embryos revealed that VGLL4 knockout embryos had reduced body size, malformed tricuspid valves, but normal myocardium and normal heart function.

This is a newly discovered function of VGLL4; this protein is needed for embryonic development, but that function is independent from and isolated from the growth of the heart's myocardial wall.

More information: Caroline Sheldon et al, Depletion of VGLL4 Causes Perinatal Lethality without Affecting Myocardial Development, Cells (2022). DOI: 10.3390/cells11182832

Provided by Masonic Medical Research Institute
Citation: New genetic finding sheds light on congenital heart disease (2022, September 21) retrieved 19 May 2024 from
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