Mice Deficient in Ribosomal Protein S6 Phosphorylation Suffer from Muscle Weakness that Reflects a Growth Defect and Energy Deficit 英文参考文献.docVIP
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Mice Deficient in Ribosomal Protein S6 Phosphorylation Suffer from Muscle Weakness that Reflects a Growth Defect and Energy Deficit 英文参考文献
MiceDeficientinRibosomalProteinS6Phosphorylation
SufferfromMuscleWeaknessthatReflectsaGrowth
DefectandEnergyDeficit
IgorRuvinsky1.¤a,MaximilianoKatz1.¤b,AvigailDreazen1,YuvalGielchinsky2,AnnSaada3 ,Nanette
Freedman4,EyalMishani4,GabrielZimmerman5,JudithKasir1,OdedMeyuhas1*
1DepartmentofBiochemistryandMolecularBiology,IMRIC,HebrewUniversity-HadassahMedicalSchool,Jerusalem,Israel,2DepartmentofObstetricsandGynecology,
Hadassah Medical Center, Jerusalem, Israel, 3Metabolic Disease Unit, Hadassah Medical Center, Jerusalem, Israel, 4Department of Medical Biophysics and Nuclear
Medicine,HadassahMedicalCenter,Jerusalem,Israel,5DepartmentofBiologicalChemistry,InstituteofLifeSciences,TheHebrewUniversity,Jerusalem,Israel
Abstract
Background:Mice,whoseribosomalproteinS6cannotbephosphorylatedduetoreplacementofallfivephosphorylatable
serine residues by alanines (rpS6P2/2), are viable and fertile. However, phenotypic characterization of these mice and
embryofibroblastsderivedfromthem,hasestablishedtheroleofthesemodificationsintheregulationofthesizeofseveral
celltypes,aswellaspancreatic b-cellfunctionandglucosehomeostasis. Arelativelypassivebehaviorofthesemicehas
raisedthepossibility thattheysufferfrommuscleweakness,whichhas,indeed,beenconfirmedbyavarietyofphysical
performancetests.
Methodology/PrincipalFindings:Alargevarietyofexperimentalmethodologies,includingmorphometricmeasurements
of histological preparations, high throughput proteomic analysis, positron emission tomography (PET) and numerous
biochemical assays, were used in an attempt to establish the mechanism underlying the relative weakness of rpS6P2/2
muscles.Collectively,theseexperimentshavedemonstratedthatthephysicalinferiorityappearstoresultfromtwodefects:
a)adecreaseintotalmusclemassthatreflectsimpairedgrowth,ratherthanaberrantdifferentiationofmyofibers,aswellas
a diminished abundance of contractile proteins; and b) a reduced content of ATP and phosphocreatine, two readily
available energy sources. The abundanc
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