Phenotyping cardiac and structural birth defects in fetal and newborn mice

Birth Defects Res. 2017 Jun 1;109(10):778-790. doi: 10.1002/bdr2.1048. Epub 2017 May 22.


Mouse models are invaluable for investigating the developmental etiology and molecular pathogenesis of structural birth defects. While this has been deployed for studying a wide spectrum of birth defects, mice are particularly valuable for modeling congenital heart disease, given they have the same four-chamber cardiac anatomy as in humans. We have developed the use of noninvasive fetal ultrasound together with micro-computed tomography (micro-CT) imaging for high throughput phenotyping of mice for congenital heart defects (CHD) and other developmental anomalies. We showed the efficacy of fetal ultrasound and micro-CT imaging for diagnosis of a wide spectrum of CHD. With fetal ultrasound, longitudinal scans can be conducted to track the developmental profile of disease pathogenesis, providing both structural information with two-dimensional (2D) imaging, as well as functional data from hemodynamic assessments with color flow and spectral Doppler imaging. In contrast, with micro-CT imaging, virtual necropsies can be conducted rapidly postmortem for diagnosis of not only CHD, but also other structural birth defects. To validate the CHD diagnosis, we further showed the use of a novel histological technique with episcopic confocal microscopy to obtain rapid 3D reconstructions for accurate diagnosis of even the most complex anatomical defect. The latter histological imaging technique when combined with the use of ultrasound and micro-CT imaging provides a powerful combination of imaging modalities that will be invaluable in meeting the accelerating demands for high throughput mouse phenotyping of genetically engineered mice in the coming age of functional genomics. Birth Defects Research 109:778-790, 2017. © 2017 Wiley Periodicals, Inc.

Keywords: congenital heart disease; fetal ultrasound imaging; forward genetic screen; micro-CT; mouse model; structural birth defects.

Publication types

  • Review

MeSH terms

  • Animals
  • Disease Models, Animal
  • Echocardiography, Doppler / methods
  • Female
  • Fetal Heart / abnormalities
  • Heart Defects, Congenital / diagnosis
  • Heart Defects, Congenital / diagnostic imaging*
  • Humans
  • Infant, Newborn
  • Mice
  • Pregnancy
  • Prenatal Care
  • Ultrasonography / methods
  • Ultrasonography, Prenatal / methods*