MYOGENIN CAN SUBSTITUTE FOR MYF5 IN PROMOTING MYOGENESIS BUT LESS EFFICIENTLY

The myogenic basic Helix-Loop-Helix transcription factors, including M yf5, MyoD, myogenin (myg) and MRF4, play important roles in skeletal m uscle development. The phenotypes of mutant mice deficient in either g ene are different, suggesting that each gene may have a unique functio n in vivo. We previously showed that targeting myogenin into the Myf5 locus (Myf5(myg-ki)) rescued the rib cage truncation in the Myf5-null mutant, hence demonstrating functional redundancy between Myf5 and myo genin in skeletal morphogenesis. Here we present the results of crossi ng myogenin knock-in (myg-ki) mice,vith either MyoD-null or myogenin-n ull mutants. The Myf5(myg-ki) allele rescued early myogenesis, but Myf 5(myg-ki/myg-ki);MyoD(-/-) mutant mice died immediately after birth ow ing to reduced muscle formation. Therefore, myogenin, expressed from t he Myf5 locus, is not able to completely replace the function of Myf5 in muscle development although it is capable of determining and/or mai ntaining myogenic lineage, Myf5(myg-ki/myg-ki);myg(-/-) mutant mice di splayed the same phenotype as myg(-/-) mutants. This indicates that th e earlier expression of myogenin cannot promote myogenic terminal diff erentiation, which is normally initiated by the endogenous myogenin. T hus, our results are consistent with the notion that Myf5 and myogenin are functionally interchangeable in determining myogenic lineage and assuring normal rib formation. Our experiment revealed, however, that some aspects of myogenesis may be unique to a given myogenic factor an d are due to either different regulatory sequences that control their temporal and spatial expression or different functional protein domain s.