Asynthetic12aminoacidsequencefromthemouseobese(Ob)gene.||Obesity,acommonnutritionaldisorder,isassociatedwithdiabetes,hypertension,hyperlipidemia,cancerandmanyotherhealthrelatedproblems.Atleastfivegenes,Obese(ob),diabetes(db),fat(fat),agoutiyellow(Ay),andtubby(tub)havebeenlinkedtoobesity.Recently,Obgenes(mouseandhuman)havebeencloned.ObesegeneencodesanADIpocyte-tissuederivedsecretedObprotein/Leptin(167aminoacid,~16kD)thatcontrolsbodyweighthomeostasis.ExogenousadmiNISTrationofrecombinantObproteincanreducefoodintakeandbodyweight.However,Obproteinhadnoeffectindb/dbmicesuggestingadefectinleptinsignalingmechanism.TheObesereceptors(Ob-R)havenowbeenclonedfrommousechoroidplexusanditisexpressedinseveraltissuesincludinghypothalamus.TheOb-Rhasbeenshowntobeaproductofdbgenethathaslongbeenthoughttoencodethereceptorforaweight-controllinghormone.TheOb-Rhasatleast6alternativelysplicedformswithmodificationsattheaminoandC-terminus(Fig2).TheOb-RvariesinlengthafterLysine889.TheOb-RarepresentstheinitiallyidentifiedmouseOb-R(shortform,894aa).Ob-Rbdisplays~78%homologytothehumanOb-R(longform,1165aa).ExpressionofOb-Rbandotherformshavebeendetectedinhypothalamusandothertissues.ThesolubleOb-Reisfoundinadiposetissues,hypothalamus,heart,andtestes.Ob-Risabnormallysplicedindb/dbmiceandmissingthecytoplasmicdomainthoughttobeimportantforleptinsignaling.

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