Identification of cardiac malformations in mice lacking Ptdsrusing a novel high-throughput magnetic resonance imaging technique

Abstract

BackgroundCongenital heart defects are the leading non-infectious cause of death in children. Genetic studies in the mouse have been crucial to uncover new genes and signaling pathways associated with heart development and congenital heart disease. The identification of murine models of congenital cardiac malformations in high-throughput mutagenesis screens and in gene-targeted models is hindered by the opacity of the mouse embryo.ResultsWe developed and optimized a novel method for high-throughput multi-embryo magnetic resonance imaging (MRI). Using this approach we identified cardiac malformations in phosphatidylserine receptor (Ptdsr) deficient embryos. These included ventricular septal defects, double-outlet right ventricle, and hypoplasia of the pulmonary artery and thymus. These results indicate that Ptdsr plays a key role in cardiac development.ConclusionsOur novel multi-embryo MRI technique enables high-throughput identification of murine models for human congenital cardiopulmonary malformations at high spatial resolution. The technique can be easily adapted for mouse mutagenesis screens and, thus provides an important new tool for identifying new mouse models for human congenital heart diseases.

Generation of histo-anatomically representative models of the individual heart: tools and application

“…The highest resolution datasets acquired were of 21.5 mm isotropic resolution for rat (data reconstructed as described before in Schneider et al 2004) and 26.4!26.4 mm in plane, 24.4 mm out of plane for rabbit (as described by Burton et al 2006).…”

VACTERL/caudal regression/Currarino syndrome-like malformations in mice with mutation in the proprotein convertasePcsk5

“…MRI and skeletal preparations were performed as described (Kaufman 1994;Schneider et al 2004). The generation of Pcsk5 flox/+ and Pcsk5 ⌬1 alleles is described elsewhere (Essalmani et al 2008).…”

JMJD8 Regulates Angiogenic Sprouting and Cellular Metabolism by Interacting With Pyruvate Kinase M2 in Endothelial Cells

“…Mice lacking JmjC proteins like Jmjd6 or the name-giving enzyme of the JmjC protein family Jarid2 (JMJ) have a disturbed cardiac development already in the embryonic stage, which potentially is the cause for pre-or postnatal lethality. [39][40][41] However, Jmjd8 −/− mice are viable and do not show an obvious phenotype, suggesting that Jmjd8 is not essential for embryonic vascular development. Nevertheless,…”