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Science 8 October 2004:
Vol. 306. no. 5694, pp. 247 - 252
DOI: 10.1126/science.1102612
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Research Articles

Rescue of Cardiac Defects in Id Knockout Embryos by Injection of Embryonic Stem Cells

Diego Fraidenraich,1 Elizabeth Stillwell,1 Elizabeth Romero,1 David Wilkes,3 Katia Manova,2 Craig T. Basson,3 Robert Benezra1*

We report that Id knockout mouse embryos display multiple cardiac defects, but mid-gestation lethality is rescued by the injection of 15 wild-type embryonic stem (ES) cells into mutant blastocysts. Myocardial markers altered in Id mutant cells are restored to normal throughout the chimeric myocardium. Intraperitoneal injection of ES cells into female mice before conception also partially rescues the cardiac phenotype with no incorporation of ES cells. Insulin-like growth factor 1, a long-range secreted factor, in combination with WNT5a, a locally secreted factor, likely account for complete reversion of the cardiac phenotype. Thus, ES cells have the potential to reverse congenital defects through Id-dependent local and long-range effects in a mammalian embryo.

1 Cancer Biology and Genetics Program, Department of Medicine, Weill Medical College of Cornell University, New York, NY 10021, USA.
2 Molecular Cytology Core Facility, Memorial Sloan-Kettering Cancer Center, Department of Medicine, Weill Medical College of Cornell University, New York, NY 10021, USA.
3 Molecular Cardiology Laboratory, Greenberg Cardiology Division, Department of Medicine, Weill Medical College of Cornell University, New York, NY 10021, USA.

* To whom correspondence should be addressed. E-mail: r-benezra{at}ski.mskcc.org

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