Functional redundancy of the muscle-specific transcription factors Myf5 and myogenin.
The myogenic basic helix-loop-helix transcription factors, Myf5, MyoD, myogenin and MRF4, play key roles in skeletal muscle development. All of them induce myogenic differentiation in cultured non-muscle cells, suggesting that they might be functionally redundant. But the genes are expressed at different times during embryogenesis and mice carrying a mutation in any of the genes have different phenotypes. A rib cage defect was observed in Myf5-deficient mice, which die perinatally. We investigated whether the rib cage defect was due to the failure of the early activation of the gene or to the unique interactions of Myf5 with specific downstream targets. For this we inserted a myogenin complementary DNA into the Myf5 locus by homologous recombination which simultaneously disrupted Myf5 function. We report here that mice homozygous for this myogenin gene knock-in (ki) developed a normal rib cage and were viable, therefore demonstrating functional redundancy of Myf5 and myogenin for rib formation.
Wang
Y
Y
Whitehead Institute for Biomedical Research, Massachusetts Institute of Technology, Cambridge, MA 02142, USA.
Schnegelsberg
P N
PN
Dausman
J
J
Jaenisch
R
R
D000818:Animals; D001483:Base Sequence; D002460:Cell Line; D017931:DNA Primers; D018076:DNA, Complementary; D004268:DNA-Binding Proteins; D018257:Helix-Loop-Helix Motifs; D051379:Mice; D008969:Molecular Sequence Data; D009124:Muscle Proteins / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D051787:Myogenic Regulatory Factor 5; D018008:Myogenin / Q000235:genetics / Q000502:physiology*; D012272:Ribs / Q000002:abnormalities / Q000196:embryology; D015534:Trans-Activators; D014157:Transcription Factors / Q000172:deficiency / Q000235:genetics / Q000502:physiology*
D017931:DNA Primers; D018076:DNA, Complementary; D004268:DNA-Binding Proteins; D009124:Muscle Proteins; C497418:Myf5 protein, mouse; C503801:Myog protein, mouse; D051787:Myogenic Regulatory Factor 5; D018008:Myogenin; D015534:Trans-Activators; D014157:Transcription Factors