OMIMOnlineMendelianInheritanceinManAll DatabasesPubMedNucleotideProteinGenomeStructurePMCTaxonomyOMIM SearchPubMedProteinNucleotideCoreNucleotideGSSESTStructureGenomeBooksCancerChromosomesConservedDomainsdbGaP3DDomainsGeneGenomeProjectGENSATGEOProfilesGEODataSetsHomoloGeneJournalsMeSHNCBIWebSiteNLMCatalogOMIAOMIMPMCPopSetProbeProteinClustersPubChemBioAssayPubChemCompoundPubChemSubstanceSNPTaxonomyToolKitUniGeneUniSTSLimitsPreview/IndexHistoryClipboardDetailsDisplayTitlesDetailedClinicalSynopsisAllelicVariantsASN1XMLLinkOutRelatedEntriesBookLinksGeneLinksGenomeLinksGEOProfileLinksHomoloGeneLinksNucleotideLinksOMIALinksPubChemBioAssayLinksPMCLinksProteinLinksPubMed(calculated)LinksPubMed(cited)LinksSNPLinksGeneGenotypeLinksStructureLinksUniGeneLinksUniSTSLinksShow5102050100200500SendtoTextFilePrinterClipboardAll1OMIMdbSNP0OMIMUniSTS1*602714LinksADISINTEGRINANDMETALLOPROTEINASEDOMAIN12ADAM12AlternativetitlessymbolsMELTRINALPHAMOUSEHOMOLOGOFMLTNGenemaplocus10q263TEXTCLONINGToisolategenesrelatedtofertilinexpressedinmuscleYagamiHiromasaetal(1995)amplifiedcDNAspreparedfromamousemyogeniccelllinebyPCRusingdegenerativeprimersforconservedaminoacidsbetweenfertilinalphaandbeta(601533)Theyidentified3novelmousesequenceswhichtheycalledmeltrinsSimilarlytomyogeninamarkerofearlymuscledifferentiationmousemeltrinalphaisexpressedinneonatalmuscleandboneanditsexpressionincreasesdramaticallyinresponsetotheinductionofdifferentiationImmunocytochemicallocalizationandfunctionalexpressionstudiessuggestedthatmeltrinalphamaybeinvolvedinmyotubeformationGilpinetal(1998)screenedayeast2hybridcDNAlibrarywithlamininbeta2(150325)cDNATheyisolatedahumangenewhichtheytermedADAM12thatisthehumanhomologofmousemeltrinalphaTheyfound2differentiallysplicedisoformsashortersecretedform(ADAM12S)andalargermembraneboundform(ADAM12L)thatdivergeattheir3primeendsADAM12Lmorecloselyresemblesmeltrinalphathemature881aminoacidproteincontainsatransmembranedomainatitsCterminusThematureADAM12S718aminoacidproteinhasnotransmembranedomainBothformscontainametalloproteasedomainadisintegrindomainandacysteinerichdomaincomponentscharacteristicoftheADAMfamilyGENEFUNCTIONGallianoetal(2000)foundbyRTPCRandimmunoblotanalysesthatexpressionofmouseAdam12increasesduringmuscleregenerationwhilethelevelsofotherADAMsremainconstantImmunofluorescenceanalysisrevealedstainingofsmallnewlyformedmusclefibersinregeneratingbutnotnormaladultmusclecellsUsingayeast2hybridscreenofahumanskeletalmusclecDNAlibrarywiththecytoplasmictailofhumanADAM12asbaitGallianoetal(2000)determinedthatthemembraneproximalportionoftheCterminalhalfofmyristoylatedADAM12interactswithmusclespecificalphaactinin2(ACTN2102573)Gallianoetal(2000)determinedthatoverexpressionofcytosolicADAM12containingtheACTN2bindingsiteinhibitsmousemyoblastfusionMAPPINGGilpinetal(1998)usedfluorescenceinsituhybridizationtomaptheADAM12genetohumanchromosome10q263RadiationhybridmappingplacedthegenebetweenmarkersD10S216andD10S575Asequencetaggedsite(WI17472)isidenticaltopartofthe3primeuntranslatedregionofADAM12ByFISHKurisakietal(2003)mappedthemouseAdam12genetotheF3distalF4bandofchromosome7ANIMALMODELBygenetargetingKurisakietal(2003)developedAdam12deficientmiceMutantembryosdevelopedattheexpectedmendelianratioshowever30%ofthenullpupsdiedbeforeweaningViablehomozygousmutantsappearednormalandwerefertileMostmusclesoftheAdam12nullmiceappearednormalandregenerationinexperimentallydamagedskeletalmusclewasunimpededInsomeAdam12nullpupstheinterscapularbrownadiposetissuewasreducedalthoughthepenetranceofthisphenotypeappearedlowImpairedformationoftheneckandinterscapularmuscleswasalsoseeninsomehomozygotesKurisakietal(2003)hypothesizedthatAdam12maybeinvolvedinregulatingadipogenesisandmyogenesisthroughalinkeddevelopmentalpathwayTheyalsofoundthatphorbolestertreatmentofculturedfibroblastsofnullembryosshowedreducedectodomainsheddingofheparinbindingepidermalgrowthfactorlikegrowthfactor(HBEGF126150)suggestingthatthisgrowthfactorisasubstrateforAdam12ADAM12overexpressionhadbeendemonstratedtopreventmusclecellnecrosisinthemdxmouse(seeDMD300377)amodelforDuchennemusculardystrophy(DMD310200)Moghadaszadehetal(2003)foundthattransgenicmiceoverexpressingADAM12exhibitedonlymildmyopathicchangesandacceleratedregenerationfollowingacuteinjuryOnlysmallchangesingeneexpressionprofileswerefoundbetweenmdx/ADAM12transgenicmiceandmdxmicesuggestingthatsignificantchangesinmdx/ADAM12musclemightoccurposttranscriptionallyByimmunostainingandimmunoblottingMoghadaszadehetal(2003)detecteda2foldincreaseinexpressionandextrasynapticlocalizationofalpha7Bintegrin(ITGA7600536)andutrophin(128240)thefunctionalhomologofdystrophinExpressionofdystrophinassociatedglycoproteinswasalsoincreasedREFERENCES1GallianoMFHuetCFrygeliusJPolgrenAWewerUMEngvallEBindingofADAM12amarkerofskeletalmuscleregenerationtothemusclespecificactinbindingproteinalphaactinin2isrequiredformyoblastfusionJBiolChem27513933139392000PubMedID107885192GilpinBJLoechelFMatteiMGEngvallEAlbrechtsenRWewerUMAnovelsecretedformofhumanADAM12(meltrinalpha)provokesmyogenesisinvivoJBiolChem2731571661998PubMedID94170603KurisakiTMasudaASudoKSakagamiJHigashiyamaSMatsudaYNagabukuroATsujiANabeshimaYAsanoMIwakuraYSeharaFujisawaAPhenotypicanalysisofmeltrinalpha(ADAM12)deficientmiceinvolvementofmeltrinalphainadipogenesisandmyogenesisMolecCellBiol2355612003PubMedID124829604MoghadaszadehBAlbrechtsenRGuoLTZaikMKawaguchiNBorupRHKronqvistPSchroderHDDaviesKEVoitTNielsenFCEngvallEWewerUMCompensationfordystrophindeficiencyADAM12overexpressioninskeletalmuscleresultsinincreasedalpha7integrinutrophinandassociatedglycoproteinsHumMolecGenet12246724792003PubMedID129154585YagamiHiromasaTSatoTKurisakiTKamijoKNabeshimaYFujisawaSeharaAAmetalloproteasedisintegrinparticipatinginmyoblastfusionNature3776526561995PubMedID7566181CONTRIBUTORSGeorgeETillerupdated9/12/2005PatriciaAHartzupdated3/10/2003PaulJConverseupdated12/4/2000CREATIONDATEJenniferPMacke6/10/1998EDITHISTORYalopez9/15/2005terry9/12/2005terry4/5/2005mgross3/12/2003terry3/10/2003mgross12/4/2000terry12/4/2000alopez12/15/1998alopez6/10/1998Copyright©19662007JohnsHopkinsUniversityDisplayTitlesDetailedClinicalSynopsisAllelicVariantsASN1XMLLinkOutRelatedEntriesBookLinksGeneLinksGenomeLinksGEOProfileLinksHomoloGeneLinksNucleotideLinksOMIALinksPubChemBioAssayLinksPMCLinksProteinLinksPubMed(calculated)LinksPubMed(cited)LinksSNPLinksGeneGenotypeLinksStructureLinksUniGeneLinksUniSTSLinksShow5102050100200500SendtoTextFilePrinterClipboardDisclaimerWritetotheHelpDeskPrivacyPolicyNCBINLMNIH