Targeted inactivation of myogenic factor genes reveals their role during mouse myogenesis: a review.
The role of the four myogenic regulating genes Myf-5, myogenin, MyoD, and MRF4 (herculin, Myf-6) during mouse embryogenesis has been investigated by targeted gene inactivation. Null mutations for the MyoD gene generate no skeletal muscle phenotype due to a compensatory activation of the Myf-5 gene. Mice carrying a homozygous Myf-5 mutation exert considerably delayed myotome formation with unexpected consequences. While skeletal myogenesis in these mutant mice resumes normally at the onset of MyoD expression, a skeletal defect of the ribs persists. Apparently, Myf-5 and MyoD individually are not absolutely essential for skeletal muscle development, most likely because they have overlapping or redundant functions. In fact, double mutants lacking both, MyoD and Myf-5, fail to develop skeletal musculature and the muscle forming regions seem to be devoid of myoblasts. Homozygous inactivation of the myogenin gene leads to drastically reduced myofiber formation. These mice accumulate apparently normal numbers of myoblasts which are arrested in their terminal differentiation program. Myf-6 null mutant mice exhibit drastically reduced expression of Myf-5 for reasons presently unknown. The phenotype is very similar to Myf-5 mutants with an additional reduction of deep back muscles and minor alterations in sarcomeric protein isoforms. Based on the phenotypes obtained from these various gene "knock-out" mice, we now begin to understand the regulatory network and the homostatic relationship of genes which are critically involved in myogenesis of vertebrates.
Arnold
H H
HH
Department of Cell and Molecular Biology, Technical University of Braunschweig, Germany.
Braun
T
T
D000818:Animals; D004268:DNA-Binding Proteins; D018507:Gene Expression Regulation, Developmental; D018390:Gene Targeting; D006720:Homozygote; D051379:Mice; D018345:Mice, Knockout; D009124:Muscle Proteins / Q000235:genetics; D018482:Muscle, Skeletal / Q000196:embryology* / Q000378:metabolism; D017570:MyoD Protein / Q000235:genetics; D051787:Myogenic Regulatory Factor 5; D018006:Myogenic Regulatory Factors / Q000235:genetics*; D018008:Myogenin / Q000235:genetics; D010641:Phenotype; D015534:Trans-Activators
D004268:DNA-Binding Proteins; D009124:Muscle Proteins; C497418:Myf5 protein, mouse; D017570:MyoD Protein; C503801:Myog protein, mouse; D051787:Myogenic Regulatory Factor 5; D018006:Myogenic Regulatory Factors; D018008:Myogenin; D015534:Trans-Activators; C063403:myogenic factor 6