Identification of cardiac malformations in mice lacking Ptdsr using a novel high-throughput magnetic resonance imaging technique.
BACKGROUND
Congenital 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.


RESULTS
We 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.


CONCLUSIONS
Our 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.
Schneider
Jürgen E
JE
Department of Cardiovascular Medicine, University of Oxford, Wellcome Trust Centre for Human Genetics, Roosevelt Drive, Oxford, OX3 7BN UK. jurgen.schneider@cardiovascular-medicine.oxford.ac.uk <jurgen.schneider@cardiovascular-medicine.oxford.ac.uk>
Böse
Jens
J
Bamforth
Simon D
SD
Gruber
Achim D
AD
Broadbent
Carol
C
Clarke
Kieran
K
Neubauer
Stefan
S
Lengeling
Andreas
A
Bhattacharya
Shoumo
S
D000818:Animals; D004062:DiGeorge Syndrome / Q000175:diagnosis; D006330:Heart Defects, Congenital / Q000175:diagnosis* / Q000209:etiology* / Q000235:genetics; D006345:Heart Septal Defects, Ventricular / Q000175:diagnosis; D006352:Heart Ventricles / Q000002:abnormalities / Q000473:pathology; D008279:Magnetic Resonance Imaging; D051379:Mice; D018345:Mice, Knockout; D023421:Models, Animal; D016296:Mutagenesis; D011956:Receptors, Cell Surface / Q000172:deficiency* / Q000235:genetics
C498708:Ptdsr protein, mouse; D011956:Receptors, Cell Surface