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

Abstract

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-em bryonic tissues.

Development and function of tissue resident macrophages in mice

“…This hypothesis is supported by the analysis of blood-circulation-deficient animals like the cardiac Na + -Ca 2+ exchanger ( Ncx1) knockout mice. Ncx1 -deficient animals die in utero at 9.5 dpc due to heart failure and lack of blood circulation (80,81) and they show an accumulation of macrophages in the YS, but a decrease of microglial cells in the developing neuroectoderm (62). Similarly, YS-EMPs are not detected in the fetal liver in Ncx1- deficient embryos, but increase massively in the YS (75).…”

Transgenic expression of Korean type hepatitis C virus core protein and related mutants in mice

“…Morphologic findings of dysplastic liver cells were characterized by cellular enlargement, nuclear pleomorphism, multinucleation and the presence of large nucleoli, occurring in groups (Watanabe et al, 1983;Cho et al, 2003).…”

Embryonic lethality inDeargene-deficient mice: new player in angiogenesis

“…While VEGF is a key regulator of vascularization in health and disease (7), the complexity of vascularization is nevertheless evident, as other key modulators of angiogenesis, defined by embryonic lethal phenotypes associated with abnormal embryonic and/or extraembryonic vascularization phenotypes, exist. These modulators represent diverse functional groups, such as transcription factors like hypoxia-inducible transcription factor (45) and HAND1 (34), energy metabolism regulators like Foxo1 (19), ion pumps like Na/Ca exchanger (9), integrins like ␤8 (58) and ␣7/␤1 integrin (17) and regulators of integrins like focal adhesion kinase (49), growth factors like transforming growth factor (TGF)-␤1 (31), signal transduction kinases like p38␣ mitogen-activated protein kinase (35) and G proteins like G␣13 (44), and signal transduction modulators like Edd, a hyperplastic disc gene (48).…”