Lrrc10 is required for early heart development and function in zebrafish.
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.
Kim
Ki-Hyun
KH
Department of Anatomy, School of Medicine and Public Health, University of Wisconsin, 1300 University Avenue, Madison, WI 53706, USA.
Antkiewicz
Dagmara S
DS
Yan
Long
L
Eliceiri
Kevin W
KW
Heideman
Warren
W
Peterson
Richard E
RE
Lee
Youngsook
Y
D000595:Amino Acid Sequence; D000818:Animals; D030801:Animals, Genetically Modified; D003001:Cloning, Molecular; D017931:DNA Primers / Q000235:genetics; D018076:DNA, Complementary / Q000235:genetics; D018507:Gene Expression Regulation, Developmental; D006321:Heart / Q000196:embryology*; D000090263:Leucine-Rich Repeat Proteins; D008969:Molecular Sequence Data; D009124:Muscle Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology*; D020319:Oligodeoxyribonucleotides, Antisense / Q000235:genetics; D009928:Organ Specificity; D011506:Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology*; D017386:Sequence Homology, Amino Acid; D015027:Zebrafish / Q000196:embryology* / Q000235:genetics / Q000502:physiology*; D029961:Zebrafish Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology*
D017931:DNA Primers; D018076:DNA, Complementary; D000090263:Leucine-Rich Repeat Proteins; D009124:Muscle Proteins; D020319:Oligodeoxyribonucleotides, Antisense; D011506:Proteins; D029961:Zebrafish Proteins