The transcription factor Gata3 is an important regulator of the development of thymus,
the nervous system, ear, kidney, and adrenal glands. This study analyzes the role
of Gata3 in the developing heart using a mouse strain containing an nlsLacZ reporter
gene fused in frame to the Gata3 gene by homologous recombination. Using in situ hybridization,
RT-PCR and Gata3-LacZ histochemistry, Gata3 expression was shown in various cardiac
structures up to newborn stage. During looping stages (E9.5-E11.5) Gata3-LacZ activity
recapitulated endogenous Gata3 and was abundantly expressed in the endocardial ridges
and endothelium of distal outflow tract. Strong reporter gene expression was also
noted in the mesenchyme of ventral branchial arches, and in the epithelium. In the
atrioventricular canal expression was relatively lower. In the four-chambered heart
stages (E13.5-E17.5) the LacZ-staining did not recapitulate the endogenous Gata3 transcript
and showed rather lineage tracing of formerly Gata3-expressing cells in the hearts.
beta-Galactosidase activity was detected in the cusps of semilunar valves, aorta,
pulmonary trunk, innominate and common carotid arteries, and faintly in the atrioventricular
valves. Gata3-null embryos die normally between E11 and E12. Pharmacological treatment
with sympathomimetic beta-adrenergic receptor agonist lengthens the survival up to
E18 when malformations of the heart such as ventricular septal defect (VSD), double-outlet
of right ventricle (DORV), anomalies of the aortic arch (AAA) and persistent truncus
arteriosus (PTA) were detected. The specified malformations correlate with the normal
developmental pattern of Gata3-LacZ expression. The short outflow tract and insufficient
rotation of truncus arteriosus during looping stages might be the main reasons underlying
these malformations.