Exp Mol Med.  2003 Apr;35(2):125-135.

Partial rescue of the Na+-Ca2+ exchanger (NCX1) knock-out mouse by transgenic expression of NCX1

Affiliations
  • 1Department of Life Science Division of Molecular and Life Science Pohang University of Science and Technology Pohang, Kyungbuk 790-784, Korea. colee@postech.ac.kr
  • 2National CRI Center for Calcium and Learning Korea Institute of Science and Technology Seoul 136-791, Korea.
  • 3UCLA School of Medicine Los Angeles, CA 90095-1760, USA.

Abstract

The null mutation of cardiac Na+-Ca2+ exchanger (NCX1) gene in mice caused death of embryo in utero at embryonic day (ED) 9.0-9.5 and this embryonic lethality appears resulted from abnormal heart development. In the present study, we investigated whether transgenic re-expression of NCX1 in mutant cardiac myocytes could rescue these lethal defects. Transgenic mice expressing the canine NCX1 in a cardiac specific manner were bred into the NCX1 knock-out background but did not prevent the fetal lethality associated with the NCX1 null allele. However, the NCX1 knock-out embryos with an NCX1 transgene survived with heart beatings until ED 10.5 which was one day longer than the survival of the NCX1 knock-out embryos (ED 9.5). At ED 10.5, however, the partially rescued NCX1 embryos might have succumbed to the lack of an organized vasculature in the yolk sacs. The placental labyrinth layer was reduced in size and largely avascular. The transgenic re-expression of NCX1 rescued heart beatings and survived longer, but was still insufficient for the mice to be completely rescued. Importantly, NCX1 was observed to express in the yolk sac and the placenta of wild type mice. The results suggest that defects in extra-embryonic compartments are causal to the lethality, and that NCX1 may play an important role in establishing vascularization in extra-embryonic tissues.

Keyword

antiporters; apoptosis; blood vessels; de-velopment; embryo and fetal; gene targeting

MeSH Terms

Animals
Embryo/*metabolism/pathology
Embryo Loss
Female
Gene Deletion
*Gene Expression
Genetic Complementation Test
Mice
Mice, Knockout
Mice, Transgenic
Myocytes, Cardiac/metabolism
Phenotype
Placenta/metabolism/pathology
Sodium-Calcium Exchanger/*genetics/*metabolism
Survival Rate
Yolk Sac/embryology/metabolism/pathology
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