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High Throughput Anatomic Screening for Structural Heart Defects in Chemically Mutagenized Mice
Author(s) -
Lo Cecilia WenYa,
Rosenthal Julia,
Leatherbury Linda,
Schramm Charlene,
Mangal Vipul,
Shen Yuan,
Pappas Matthew,
Yu Qing
Publication year - 2006
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.20.5.a1301-c
Subject(s) - throughput , high throughput screening , computational biology , biology , genetics , medicine , computer science , telecommunications , wireless
We conducted a high throughput fetal ultrasound screen of ethylnitrosurea (ENU) mutagenized mice to recover mutations causing congenital heart defects (CHD). This screen yielded mutants exhibiting a wide range of cardiovascular anomalies. To diagnose the specific structural heart defects in these mutants, we utilized episcopic fluorescence image capture (EFIC), a histological technique based on tissue autofluorescence. EFIC imaging provides well registered two dimensional (2D) image stacks that can be virtually resectioned in any plane, and they also are easily 3D rendered. Thus EFIC is an ideal tool for visualizing the complex and dynamic anatomical changes occurring during heart development. To assist in the evaluation of structural heart defects, we constructed an EFIC atlas of normal mouse cardiovascular development, spanning embryonic day 9.5 to birth. It includes 2D image stacks in three orthogonal views and 3D reconstructions that together allow visualization of all of the major structures of the heart. We further show the use of EFIC imaging in the diagnosis of complex structural heart defects in several ENU mutant mouse models. One mutant was diagnosed with defect in the single ventricle spectrum together with malalignment of the great arteries, and another was diagnosed with a criss‐cross heart characterized by superior‐inferior ventricles and heart situs anomalies. Overall, these studies show the efficacy of fetal ultrasound in conjunction with EFIC imaging in the systematic and high throughput analysis of complex structural heart defects in the mammalian fetus.