What cardiovascular defect does my prenatal mouse mutant have, and why?

Abstract

Since the advent of mouse targeted mutations, gene traps, an escalating use of a variety of complex transgenic manipulations, and large-scale chemical mutagenesis projects yielding many mutants with cardiovascular defects, it has become increasingly evident that defects within the heart and vascular system are largely responsible for the observed in utero lethality of the embryo and early fetus. If a transgenically altered embryo survives implantation but fails to be born, it usually indicates that there is some form of lethal cardiovascular defect present. A number of embryonic organ and body systems, including the central nervous system, gut, lungs, urogenital system, and musculoskeletal system appear to have little or no survival value in utero (Copp, 1995). Cardiovascular abnormalities include the failure to establish an adequate yolk-sac vascular circulation, which results in early lethality (E8.5-10.5); poor cardiac function (E9.0-birth); failure to undergo correct looping and chamber formation of the primitive heart tube (E9.0-11.0); improper septation, including division of the common ventricle and atria and the establishment of a divided outflow tract (E11.0-13.0); inadequate establishment of the cardiac conduction system (E12.0-birth); and the failure of the in utero cardiovascular system to adapt to adult life (birth) and close the interatrial and aorta-pulmonary trunk shunts that are required for normal fetal life. Importantly, the developmental timing of lethality is usually a good indicator of both the type of the cardiovascular defect present and may also suggest the possible underlying cause/s. The purpose of this review is both to review the literature and to provide a beginner's guide for analysing cardiovascular defects in mouse mutants.

Calcineurin signaling in avian cardiovascular development

“…Together, these studies support a critical role for calcineurin signaling and NFAT activation in the maturation of cardiomyoctes at E3-E4 in avian embryos and E10.5-E11.5 in mice. These are comparable stages in terms of development of the heart and have been identified as critical time points for the initiation of effective blood circulation in both species (Burggren et al, 2000;Conway et al, 2003).…”

Embryonic arrest at midgestation and disruption of Notch signaling produced by the absence of both epsin 1 and epsin 2 in mice

“…Epsin DKO embryos die at E9.5-E10, i.e., at the beginning of organogenesis, when lethality if often due to vasculature defects, including inability to establish an adequate yolk-sac circulation, heart tube formation defects, and cardiac failure (40,41). Accordingly, in DKO embryos, placenta, and yolk-sac display massive angiogenesis defects.…”

Methionine synthase reductase deficiency results in adverse reproductive outcomes and congenital heart defects in mice

“…Five of the fifteen embryos identified with VSD were also developmentally delayed, presenting the possibility that incomplete septation (due to overall delay) was incorrectly identified as a VSD. However, this is unlikely since the embryos were delayed by only 0.5-1 day and ventricular septation is normally complete by E13.0 [27]. Whether the enhanced resorption rate of Mtrr gt/gt mothers may be attributed to the cardiac defects in their offspring remains a question.…”

“…Whether the enhanced resorption rate of Mtrr gt/gt mothers may be attributed to the cardiac defects in their offspring remains a question. Although VSDs are not generally embryonic lethal, severely thinned myocardium can lead to heart failure and embryonic lethality between E10.5 and E13.5 [27].…”