Partial rescue of the Na+-Ca2+ exchanger (NCX1) knock-out mouse by transgenic expression of NCX1.
The null mutation of cardiac Na(+)-Ca(2+) 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.
Cho
Chung-Hyun
CH
Department of Life Science, Pohang University of Science and Technology, Pohang, Kyungbuk 790-784, Korea.
Lee
So-Young
SY
Shin
Hee-Sup
HS
Philipson
Kenneth D
KD
Lee
Chin O
CO
D000818:Animals; D020964:Embryo Loss; D004622:Embryo, Mammalian / Q000378:metabolism* / Q000473:pathology; D005260:Female; D017353:Gene Deletion; D015870:Gene Expression; D005816:Genetic Complementation Test; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D032383:Myocytes, Cardiac / Q000378:metabolism; D010641:Phenotype; D010920:Placenta / Q000378:metabolism / Q000473:pathology; D019831:Sodium-Calcium Exchanger / Q000235:genetics* / Q000378:metabolism*; D015996:Survival Rate; D015017:Yolk Sac / Q000196:embryology / Q000378:metabolism / Q000473:pathology
D019831:Sodium-Calcium Exchanger