Animal Models of Muscular Dystrophies

摘要

Recentadvancesinmolecularbiologyhaveindicatedthatmanymutantanimalmodelsofmusculardystrophysharecommongeneticandproteinabnormalitiessimilartothoseofthehumandisease.ThebestexampleisamodelofDuchennemusculardystrophy(DMD),themdxmouse.SimilartodystrophicmuscleinDMDpatients,dystrophinproteinisnotexpressedalongthesurfacemembrane,eventhoughthemdxmousehasnoapparentsignsofmusculardysfunction.Becauseclinicalandpathologicfindingsinthedystrophic(mxd)dogaresimilartothoseinDMDpatients,italsohasbeenregardedasagoodmodelfortherapeutictrials.Thebestknownandmostextensivelystudieddy+/dy+mouselacksmerosin(laminin2),whichisonesubunitofabasementmembraneprotein,laminin.Becauseapproximatelyhalfofallpatientswiththeclassicalformofcongenitalmusculardystrophyalsolackmerosin,availabilityofthisanimalhasrevivedinterestinthestudyofthepathologicmechanismoffibernecrosisresultingfromthismembranedefect.Thedystrophichamsterisamodeloflimb-girdlemusculardystrophywithsarcoglycandeficiencyinwhichoneofthedystrophin-associatedglycoproteins,-sarcoglycan,isdefective.Becausetheseanimalmodelshavecommonproteinandgeneticdefectssimilartothoseseeninpeoplewithmusculardystrophies,theyhavebeenwidelyusedtoexaminetheeffectivenessofgenetherapyandtheadministrationofpharmacologicandtrophicfactors.