REGENERATION AND MYOGENIC CELL-PROLIFERATION CORRELATE WITH TAURINE LEVELS IN DYSTROPHIN-DEFICIENT AND MYOD-DEFICIENT MUSCLES

This study coupled proton magnetic resonance spectroscopy (H-1-NMR) an d in situ hybridization plus autoradiography in a novel examination of different phenotypes of adult myogenesis that arise from genetic disr uptions in mice. Study of muscle extracts from normal and dystrophin-d eficient mdx limb and diaphragm muscles confirmed our previous finding s linking taurine and muscle regeneration at the peak of damage and re pair. H-1-NMR distinguished biochemical differences in regenerating mu scles 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(-/-) stra in lacking expression of both MyoD and dystrophin. We tested the hypot hesis that differences in spectra according to genotype and the regene ration phenotype are related specifically to proliferation by committe d myogenic precursor cells. H-1-NMR distinguished the three mutant str ains: Taurine was highest in mdx: muscles, with the phenotype of most effective regeneration; lowest in MyoD(-/-) muscles, with the least ef fective formation of new muscle in repair, as reported previously; and intermediate in double-mutant muscles, now reported to show an interm ediate repair phenotype. The early and late muscle precursors (mpcs) e xpressing myf5 and myogenin were examined for proliferation. Eighteen percent of mdx myf5-positive mpcs were proliferative, whereas myf5-pos itive mpcs did not proliferate in regenerating muscles that lacked Myo D 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. Ther efore, the extent of accumulated structural regeneration, taurine leve ls, and proliferation of late mpc (expressing myogenin) were congruent across genotypes. Proliferation by early mpc (expressing myf5) was in hibited by the lack of MyoD expression during muscle regeneration. The se studies indicate the potential for H-1-NMR monitoring of muscle sta tus in disease, regeneration, and treatment. Anat. Rec. 252:311-324, 1 998. (C) 1998 Wiley-Liss, Inc.