PUBLICATION

Heart-specific expression of laminopathic mutations in transgenic zebrafish

Authors
Verma, A.D., Parnaik, V.K.
ID
ZDB-PUB-170504-11
Date
2017
Source
Cell biology international   41(7): 809-819 (Journal)
Registered Authors
Parnaik, Veena K., Verma, Ajay D.
Keywords
Cardiac models, cardiomyopathy, heart regeneration, lamin A, laminopathy
MeSH Terms
  • Amino Acid Sequence
  • Animals
  • Animals, Genetically Modified
  • Cell Nucleus/metabolism
  • Conserved Sequence
  • DNA, Complementary/genetics
  • Gene Expression
  • Heart/embryology
  • Heart/physiology*
  • Humans
  • Lamin Type A/genetics*
  • Lamin Type A/metabolism*
  • Mutation*
  • Myocardium/metabolism*
  • Myocytes, Cardiac/metabolism
  • Promoter Regions, Genetic
  • Zebrafish
PubMed
28464412 Full text @ Cell Biol. Int.
Abstract
Lamins are key determinants of nuclear organization and function in the metazoan nucleus. Mutations in human lamin A cause a spectrum of genetic diseases that affect cardiac muscle and skeletal muscle as well as other tissues. A few laminopathies have been modeled using the mouse. As zebrafish is a well established model for the study of cardiac development and disease, we have investigated the effects of heart-specific lamin A mutations in transgenic zebrafish. We have developed transgenic lines of zebrafish expressing conserved lamin A mutations that cause cardiac dysfunction in humans. Expression of zlamin A mutations Q291P and M368K in the heart was driven by the zebrafish cardiac troponin T2 promoter. Homozygous mutant embryos displayed nuclear abnormalities in cardiomyocyte nuclei. Expression analysis showed the upregulation of genes involved in heart regeneration in transgenic mutant embryos and a cell proliferation marker was increased in adult heart tissue. At the physiological level, there was deviation of up to 20% from normal heart rate in transgenic embryos expressing mutant lamins. Adult homozygous zebrafish were fertile and did not show signs of early mortality. Our results suggest that transgenic zebrafish models of heart-specific laminopathies show cardiac regeneration and moderate deviations in heart rate during embryonic development.
Genes / Markers
Figures
Show all Figures
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping