Myogenin Regulates Exercise Capacity but Is Dispensable for Skeletal Muscle Regeneration in Adult mdx Mice 英文参考文献.docVIP

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Myogenin Regulates Exercise Capacity but Is Dispensable for Skeletal Muscle Regeneration in Adult mdx Mice 英文参考文献.doc

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Myogenin Regulates Exercise Capacity but Is Dispensable for Skeletal Muscle Regeneration in Adult mdx Mice 英文参考文献

MyogeninRegulatesExerciseCapacitybutIsDispensable forSkeletalMuscleRegenerationinAdultmdxMice EricMeadows1,2.,JesseM.Flynn1,2.,WilliamH.Klein1* 1DepartmentofBiochemistryandMolecularBiology,TheUniversityofTexasMDAndersonCancerCenter,Houston,Texas,UnitedStatesofAmerica,2GraduateTraining PrograminGenesandDevelopment,TheUniversityofTexasSchoolofBiomedicalSciencesatHouston,Houston,Texas,UnitedStatesofAmerica Abstract Duchenne muscular dystrophy (DMD) is the most prevalent inherited childhood muscle disorder in humans. mdx mice exhibit a similar pathophysiology to the human disorder allowing for an in-depth investigation of DMD. Myogenin, a myogenicregulatoryfactor,isbestknownforitsroleinembryonicmyogenesis,butitsroleinadultmusclemaintenance andregenerationisstillpoorlyunderstood.Here,wegeneratedanmdx:Myogflox/floxmouseharboringatamoxifen-inducible Crerecombinasetransgene,whichwasusedtoconditionallydeleteMyogduringadultlife.Aftertamoxifentreatment,three groups of mice were created tostudy the effects of Myog deletion: mdx:Myogflox/flox mice (mdx), Myogflox/flox mice (wild- type), and mdx:MyogfloxD/floxD:Cre-ER mice (mdx:Myog-deleted). mdx:Myog-deleted mice exhibited no adverse phenotype andbehavednormally.Whenruntoexhaustion,mdx:Myog-deletedmicedemonstratedanenhancedcapacityforexercise compared to mdx mice, running nearly as far as wild-type mice. Moreover, these mice showed the same signature characteristics of muscle regeneration as mdx mice. Unexpectedly, wefoundthat myogenin wasdispensable for muscle regeneration.Factorsassociatedwithmusclefatigue,metabolism,andproteolysisweresignificantlyalteredinmdx:Myog- deletedmice,andthismightcontributetotheirincreasedexercisecapacity.Ourresultsrevealnovelfunctionsformyogenin inadultmuscleandsuggestthatreducingMyogexpressioninothermusclediseasemodelsmaypartiallyrestoremuscle function. Citation: Meadows E, Flynn JM, Klein WH (2011) Myogenin Regulates Exercise Capacity but Is Dispensable for Skeletal Muscle Regeneration in Adult