PUBLICATION

Lrrc10 is required for early heart development and function in zebrafish

Authors
Kim, K.H., Antkiewicz, D.S., Yan, L., Eliceir, K.W., Heideman, W., Peterson, R.E., and Lee, Y.
ID
ZDB-PUB-070711-20
Date
2007
Source
Developmental Biology   308(2): 494-506 (Journal)
Registered Authors
Heideman, Warren, Peterson, Richard E.
Keywords
Leucine-rich Repeat Containing protein 10, Heart development, Cardiac function, Zebrafish embryos, Cardiac looping defects, Pericardial edema
MeSH Terms
  • Amino Acid Sequence
  • Animals
  • Animals, Genetically Modified
  • Cloning, Molecular
  • DNA Primers/genetics
  • DNA, Complementary/genetics
  • Gene Expression Regulation, Developmental
  • Heart/embryology*
  • Molecular Sequence Data
  • Muscle Proteins/antagonists & inhibitors
  • Muscle Proteins/genetics
  • Muscle Proteins/physiology*
  • Oligodeoxyribonucleotides, Antisense/genetics
  • Organ Specificity
  • Proteins/antagonists & inhibitors
  • Proteins/genetics
  • Proteins/physiology*
  • Sequence Homology, Amino Acid
  • Zebrafish/embryology*
  • Zebrafish/genetics
  • Zebrafish/physiology*
  • Zebrafish Proteins/antagonists & inhibitors
  • Zebrafish Proteins/genetics
  • Zebrafish Proteins/physiology*
PubMed
17601532 Full text @ Dev. Biol.
Abstract
Leucine-rich Repeat Containing protein 10 (LRRC10) has recently been identified as a cardiac-specific factor in mice. However, the function of this factor remains to be elucidated. In this study, we investigated the developmental roles of Lrrc10 using zebrafish as an animal model. Knockdown of Lrrc10 in zebrafish embryos (morphants) using morpholinos caused severe cardiac morphogenic defects including a cardiac looping failure accompanied by a large pericardial edema, and embryonic lethality between day 6 and 7 post fertilization. The Lrrc10 morphants exhibited cardiac functional defects as evidenced by a decrease in ejection fraction and cardiac output. Further investigations into the underlying mechanisms of the cardiac defects revealed that the number of cardiomyocyte was reduced in the morphants. Expression of two cardiac genes was deregulated in the morphants including an increase in atrial natriuretic factor, a hallmark for cardiac hypertrophy and failure, and a decrease in cardiac myosin light chain 2, an essential protein for cardiac contractility in zebrafish. Moreover, a reduced fluorescence intensity from NADH in the morphant heart was observed in live zebrafish embryos as compared to control. Taken together, the present study demonstrates that Lrrc10 is necessary for normal cardiac development and cardiac function in zebrafish embryos, which will enhance our understanding of congenital heart defects and heart disease.
Genes / Markers
Figures
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Expression
Phenotype
Mutation and Transgenics
Human Disease / Model Data
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping
Errata and Notes