Rescue of cardiac defects in id knockout embryos by injection of embryonic stem cells.
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.
Cancer Biology and Genetics Program, Department of Medicine, Weill Medical College of Cornell University, New York, NY 10021, USA.
Diego
D
Fraidenraich
Elizabeth
E
Stillwell
Elizabeth
E
Romero
David
D
Wilkes
Katia
K
Manova
Craig T
CT
Basson
Robert
R
Benezra
D000818:Animals; D001755:Blastocyst; D002455:Cell Division; D002478:Cells, Cultured; D004268:DNA-Binding Proteins / Q000235:genetics; D020964:Embryo Loss; D004622:Embryo, Mammalian / Q000166:cytology*; D005260:Female; D020869:Gene Expression Profiling; D018507:Gene Expression Regulation, Developmental; D006321:Heart / Q000196:embryology*; D006330:Heart Defects, Congenital / Q000196:embryology / Q000628:therapy*; D051798:Inhibitor of Differentiation Protein 1; D051797:Inhibitor of Differentiation Protein 2; D007334:Insulin-Like Growth Factor I / Q000235:genetics / Q000502:physiology; D008431:Maternal-Fetal Exchange; D051379:Mice; D018345:Mice, Knockout; D009206:Myocardium / Q000166:cytology / Q000378:metabolism; D032383:Myocytes, Cardiac / Q000166:cytology; D020411:Oligonucleotide Array Sequence Analysis; D010496:Pericardium / Q000196:embryology / Q000378:metabolism; D011247:Pregnancy; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000502:physiology; D012097:Repressor Proteins / Q000235:genetics; D033581:Stem Cell Transplantation; D013234:Stem Cells / Q000502:physiology*; D014157:Transcription Factors / Q000235:genetics; D051153:Wnt Proteins; D000071818:Wnt-5a Protein
D004268:DNA-Binding Proteins; C497455:Idb1 protein, mouse; C497452:Idb2 protein, mouse; D051798:Inhibitor of Differentiation Protein 1; D051797:Inhibitor of Differentiation Protein 2; D011518:Proto-Oncogene Proteins; D012097:Repressor Proteins; D014157:Transcription Factors; D051153:Wnt Proteins; D000071818:Wnt-5a Protein; C438615:Wnt5a protein, mouse; D007334:Insulin-Like Growth Factor I