The Charles River “Hairless” Rat Mutation is Distinct from the Hairless Mouse Alleles

摘要

TheCharlesRiver(CR)#8220;hairless#8221;ratisoneoftheautosomalrecessivehypotrichoticanimalmodelsactivelystudiedinpharmacologicanddermatologicresearch.Despiteitswidespreaduse,themolecularbasisofthismonogenicmutationremainsunknown,andtheskinhistologicfeaturesofthisphenotypehaveneverbeendescribed.However,thedesignation#8220;hairless#8221;hasbeenusedasanextensionofthehairlessmouse(hr)nomenclatureonthebasisoftheclinicalabsenceofhairsinbothphenotypes.WepresentadescriptionofthehistopathologicchangesinheterozygousandhomozygousCRhairlessratmutantsduringthefirstmonthoflife.Thepostnatalhomozygousratskinwascharacterizedbyabnormalkeratinizationofthehairshaftandformationofathickanddenselayerofcorneocytesinthelowerportionoftheepidermalstratumcorneum.Thislayerpreventedtheimproperlykeratinizedhairshaftfrompenetratingtheskinsurface.Startingfromthelateststagesofhairfollicle(HF)development,obvioussignsofHFdegenerationwereobservedinhomozygousskin.Thisprocesswasextremelyrapid,andbyday12,mainlyatrophicHFswithabnormalorbrokenhairswerepresentintheskin.Therefore,themutationintheCRratabrogatescellproliferationinthehairmatrixandaffectskeratinocytedifferentiationintheHFandinterfollicularepidermis,aphenotypethatiscompletelydistinctfromhr/hr.TotestwhethertheCRratharboredamutationinthehrgene,weanalyzedthecodingregionofthisgeneandconsensusintronsplicesitesequencesinmutantratsandfoundnomutation,furthersupportingphenotypicevidencethatthehairlessphenotypeinCRratsisnotallelicwithhairless.Finally,usingintragenicpolymorphisms,wewereabletoexcludehomozygosityatthehairlesslocusbyuseofgenotypicanalysis.Thus,morphologicanalysisofsuccessivestagesofphenotypedevelopmentintheCRhairlessrat,togetherwithdefinitivemolecularstudies,indicatethatthismutationmaybeuniqueamongtheotherhypotrichoticratmutations.