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This Article Full Text Full Text (PDF) All Versions of this Article: JME-09-0030v1 43/4/157    most recent Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Google Scholar Articles by Thurisch, B. Articles by Dame, C. PubMed PubMed Citation Articles by Thurisch, B. Articles by Dame, C.

Department of Neonatology, Charité-Universitätsmedizin Berlin, Campus Virchow-Klinikum, Augustenburger Platz 1, D-13353 Berlin, Germany
¹ Department of Biochemistry and Molecular Biology, University of Florida, Gainesville, Florida 32610, USA
² Institute of Pathology, Charité-Universitätsmedizin Berlin, D-10117 Berlin, Germany
³ Institute for Experimental Endocrinology, Charité-Universitätsmedizin Berlin, D-13353 Berlin, Germany

(Correspondence should be addressed to C Dame; Email: christof.dame{at}charite.de)

*(C Dame and J Bungert designed the research work and contributed equally to this work)

Homozygous deficiency of the transcription factor Gata4 in mice causes lethality due to defects in ventral morphogenesis and heart tube formation. There is increasing evidence demonstrating that GATA4 function is also relevant for normal developed organ systems, including the heart and endocrinum. To analyze the implication of Gata4 beyond development, we generated transgenic mice expressing inducible small interfering RNA against Gata4. In longitudinal analysis, efficient suppression of Gata4 mRNA (down to 80% of wild-type levels) and protein expression in the heart was detected 38 days after induction of Gata4 short hairpin RNA. Decreased Gata4 expression was associated with reduction in the expression of known cardiac target genes, but the function of the heart remained unperturbed at 20–30% of normal Gata4 levels. Interestingly, Gata4 expression was almost abolished in the ovary and testis. This was accompanied in the testis by a significant reduction of GATA4 downstream target genes, such as the genes encoding Mullerian inhibiting substance (MIS) and steroidogenic acute regulatory (StAR) protein. By contrast, expression levels of Mis and Star were only slightly modified in the ovary, and concentrations of circulating FSH and LH were normal in female transgenic mice after induction of Gata4 short hairpin RNA. However, inhibition of Gata4 expression led to the formation of ovarian teratoma in 10% of females. Histology of the teratomas showed predominantly ectodermal and mesodermal structures. Our data demonstrate that Gata4 is critically involved in the function and integrity of the gonads in vivo.