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(Circulation. 2000;101:178.)
© 2000 American Heart Association, Inc.

Basic Science Reports

High-Efficiency, Long-Term Cardiac Expression of Foreign Genes in Living Mouse Embryos and Neonates

Geir Christensen, MD, PhD; Susumu Minamisawa, MD, PhD; Peter J. Gruber, MD, PhD; Yibin Wang, PhD; Kenneth R. Chien, MD, PhD

From the UCSD-Salk Program in Molecular Genetics, Department of Medicine and Center for Molecular Genetics, University of California San Diego, La Jolla (G.C., S.M., P.J.G., Y.W., K.R.C.); the Institute for Experimental Medical Research, University of Oslo, Ullevaal Hospital, Oslo, Norway (G.C.); the Division of Cardiac Surgery, Johns Hopkins Hospital, Baltimore, Md (P.J.G.); and the Department of Physiology, University of Maryland School of Medicine, Baltimore (Y.W.).

Correspondence to Dr Geir Christensen, Institute for Experimental Medical Research, University of Oslo, Ullevaal Hospital, N-0407 Oslo, Norway. E-mail geir.christensen{at}ioks.uio.no

Background—The development of improved strategies for efficient and reproducible in vivo gene transfer into the murine heart will ultimately allow the intersection of somatic and germline gene transfer strategies to study complex features of cardiac biology and diseases.

Methods and Results—For embryonic gene transfer, an adenovirus vector expressing ß-galactosidase was injected in utero into the ventricular cavity of living embryos via microsurgical approaches. The injected embryos were developed to term, and efficient expression of the transgene was detected in all cell types in the heart. For postnatal cardiac gene transfer, adenovirus was injected into the cardiac ventricle of neonatal mice, resulting in efficient expression of the transgene in the outer layer of the myocardium as well as cardiomyocytes in the middle and inner layers of the cardiac wall. Mice examined after 3 weeks displayed a pattern of expression that completely mimicked the pattern seen after 3 days, and gene expression was also found after 6 months. The infected myocytes can be identified by coinfection of an adenovirus expressing green fluorescent protein without affecting their normal physiological function.

Conclusions—We have developed a new strategy to achieve efficient and long-term foreign gene expression in both embryonic and postnatal mouse myocardium via direct intracardiac injection of recombinant adenovirus. The strategy should allow the functional assessment of the expression of dominantly acting exogenous genes, overexpression of wild-type genes, and Cre recombinase–mediated gene ablations at the single-cell level in the context of the intact adult mouse myocardium.

Key Words: myocytes • viruses • proteins • myocardium

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