Regeneration and myogenic cell proliferation correlate with taurine levels in dystrophin- and MyoD-deficient muscles.
This study coupled proton magnetic resonance spectroscopy (1H-NMR) and in situ hybridization plus autoradiography in a novel examination of different phenotypes of adult myogenesis that arise from genetic disruptions in mice. Study of muscle extracts from normal and dystrophin-deficient mdx limb and diaphragm muscles confirmed our previous findings linking taurine and muscle regeneration at the peak of damage and repair. 1H-NMR distinguished biochemical differences in regenerating muscles that were consistent with the extent of repair in three strains: mdx dystrophic mice; MyoD(-/-) mice that lack expression of the early myogenic regulatory gene MyoD; and a double-mutant mdx:MyoD(-/-) strain lacking expression of both MyoD and dystrophin. We tested the hypothesis that differences in spectra according to genotype and the regeneration phenotype are related specifically to proliferation by committed myogenic precursor cells. 1H-NMR distinguished the three mutant strains: Taurine was highest in mdx muscles, with the phenotype of most effective regeneration; lowest in MyoD(-/-) muscles, with the least effective formation of new muscle in repair, as reported previously; and intermediate in double-mutant muscles, now reported to show an intermediate repair phenotype. The early and late muscle precursors (mpcs) expressing myf5 and myogenin were examined for proliferation. Eighteen percent of mdx myf5-positive mpcs were proliferative, whereas myf5-positive mpcs did not proliferate in regenerating muscles that lacked MyoD expression. By contrast, whereas 30% of myogenin-positive mpcs were proliferative in mdx muscles, almost none were proliferative in MyoD(-/-) muscles, and 12% were proliferative in double-mutant muscles. Therefore, the extent of accumulated structural regeneration, taurine levels, and proliferation of late mpc (expressing myogenin) were congruent across genotypes. Proliferation by early mpc (expressing myf5) was inhibited by the lack of MyoD expression during muscle regeneration. These studies indicate the potential for 1H-NMR monitoring of muscle status in disease, regeneration, and treatment.
McIntosh
L M
LM
Institute for Biodiagnostics, National Research Council of Canada, Winnipeg, Manitoba.
Garrett
K L
KL
Megeney
L
L
Rudnicki
M A
MA
Anderson
J E
JE
D000818:Animals; D001345:Autoradiography; D002452:Cell Count; D002455:Cell Division / Q000502:physiology; D003444:Crush Syndrome / Q000378:metabolism / Q000473:pathology; D016189:Dystrophin / Q000172:deficiency / Q000235:genetics*; D017353:Gene Deletion; D017403:In Situ Hybridization; D009682:Magnetic Resonance Spectroscopy; D051379:Mice; D018101:Mice, Inbred mdx; D008817:Mice, Mutant Strains; D018482:Muscle, Skeletal / Q000293:injuries / Q000378:metabolism* / Q000473:pathology; D009137:Muscular Dystrophy, Animal / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D017570:MyoD Protein / Q000235:genetics*; D009206:Myocardium / Q000473:pathology; D012038:Regeneration / Q000502:physiology*; D013654:Taurine / Q000378:metabolism*
D016189:Dystrophin; D017570:MyoD Protein; D013654:Taurine