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LDB Mouse ENU Mutagenesis Program

The Laboratory of Developmental Biology initiated on June 2002, a mouse ENU Mutagenesis Program. The goal of this program is to use noninvasive ultrasound imaging to conduct a noninvasive in utero screen of ENU mutagenized mice to recover mouse mutations causing congenital heart anomalies. As of August 15, 2003, 3869 fetuses have been screened from 529 G2 females encompassing nearly 200 families, yielding a high incidence of cardiovascular anomalies (see Summary of Mutagenesis Screening). This work is being conducted in collaboration with the Jackson Laboratory, under the auspices of a guest investigator program funded by the NHLBI Program for Genomic Applications.

For this screen, C57BL6/J mice are ENU mutagenized and bred using a backcrossing scheme designed for the retrieval of recessive mutations. Non-invasive in utero fetal ultrasound imaging was used for this study and includes 2D imaging, spectral Doppler analysis, color flow Doppler, and M-mode imaging. Fetuses are scanned from E12.5 to E19.5 (birth), with most scanned horizontally at two or three different developmental stages. Overall, the gross defects that can be detected by ultrasound include prenatal lethality, growth retardation, and cardiovascular defects. Cardiovascular defects that can be ultrasound diagnosed including arrhythmia, heart failure, high outflow velocity, outflow regurgitation, hypertrophy and ectopia cordis.

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