ALTERATION OF MYOGENIC REGULATORY COMPONENTS IN A RAT MYOBLAST GLUT3(-) MUTANT

Myogenesis is a complex process characterized by both biochemical and morphological differentiation. Recent transfection studies suggested a close relationship between the GLUT 3 transporter and the myogenic ab ility of rat skeletal L6 myoblast. In this study, the myogenic propert ies of GLUT 3(-) mutants were examined. Studies using three different GLUT 3(-) mutants (D2, D9 and D23) revealed that these mutants were de fective not only in the GLUT 3 transporter, but also in the expression of myogenesis-associated genes. The properties of mutant D23 were fur ther characterized. Overexpression of an exogenous functional GLUT 3 t ransporter was unable to restore the myogenic defects of this mutant. This mutant was subsequently found to be altered in components acting on at least two different sites of the L6 myogenic pathway. Transfecti on studies revealed that mutant D23 was deficient in component(s) esse ntial for the myogenin promoter activity. The second component was req uired for the transcription of muscle-specific protein genes, as overe xpression of myogenin was unable to rescue the inability of this mutan t to express muscle-specific genes and to form myotubes. Mutant D23 wa s therefore thought to be deficient in a regulatory component which co ntrolled the expression of GLUT 3, myogenin and muscle-specific genes. (C) 1998 Elsevier Science B.V. All rights reserved.