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

• Published in: Science (American Association for the Advancement of Science) 2004-10, Vol.306 (5694), p.247-252
• Main Authors: Fraidenraich, Diego, Stillwell, Elizabeth, Romero, Elizabeth, Wilkes, David, Manova, Katia, Basson, Craig T., Benezra, Robert
• Format: Article
• Language: English
• Subjects: Animals; Biological and medical sciences; Birth defects; Blastocyst; Cardiology; Cell Division; Cell growth; Cells, Cultured; Classical genetics, quantitative genetics, hybrids; DNA-Binding Proteins - genetics; Embryo Loss; Embryo, Mammalian - cytology; Embryonic stem cells; Embryos; Endocardium; Endothelial cells; Epicardium; Female; Fundamental and applied biological sciences. Psychology; Gene Expression Profiling; Gene Expression Regulation, Developmental; Genetic aspects; Genetics of eukaryotes. Biological and molecular evolution; Heart; Heart - embryology; Heart Defects, Congenital - embryology; Heart Defects, Congenital - therapy; Individualized Instruction; Inhibitor of Differentiation Protein 1; Inhibitor of Differentiation Protein 2; Insulin-Like Growth Factor I - genetics; Insulin-Like Growth Factor I - physiology; Maternal-Fetal Exchange; Mice; Mice, Knockout; Myocardium; Myocardium - cytology; Myocardium - metabolism; Myocytes, Cardiac - cytology; Oligonucleotide Array Sequence Analysis; Pathology; Pericardium - embryology; Pericardium - metabolism; Physiological aspects; Pollution; Pregnancy; Proto-Oncogene Proteins - genetics; Proto-Oncogene Proteins - physiology; Pups; Repressor Proteins - genetics; Rodents; Stem Cell Transplantation; Stem cells; Stem Cells - physiology; Transcription Factors - genetics; Vertebrata; Wnt Proteins; Wnt-5a Protein
• ISSN: 0036-8075; 1095-9203
• DOI: 10.1126/science.1102612

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.