PNAS-2013-Zhang-1220712110

PNAS-2013-Zhang-1220712110

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时间:2019-07-20

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1、Serotoninsignalinginthebrainofadultfemalemiceisrequiredforsexualpreferencea,b,1a,b,1a,b,2ShashaZhang,YanLiu,andYiRaoaStateKeyLaboratoryofBiomembraneandMembraneBiotechnologyandPeking-TsinghuaCenterforLifeSciences,SchoolofLifeSciences,andPekingbUniversity-InternationalDataGroup-McGovernInstitut

2、eforBrainResearch,PekingUniversity,Beijing100871,China;andNationalInstituteofBiologicalSciences,Beijing102206,ChinaEditedbyCatherineG.Dulac,HarvardUniversity,Cambridge,MA,andacceptedbytheEditorialBoardApril30,2013(receivedforreviewNovember30,2012)Aroleforserotonininmalesexualpreferencewasrece

3、ntlyResultsuncoveredbyourfindingthatmalemutantmicelackingserotoninFemaleMiceLackingSerotonergicNeuronsPreferredFemaleOverhavelostsexualpreference.HereweshowthatfemalemouseMaleMice.ItwasknownthatconditionalLIMhomeoboxtran-mutantslackingeithercentralserotonergicneuronsorserotoninscriptionfactor1

4、-beta(Lmx1b)knockoutmice(Lmx1b−/−)couldpreferfemaleovermalegenitalodorswhengivenachoice,andbegeneratedbycrossingCrerecombinasedrivedbyPet-1enhancerdisplayedincreasedfemale–femalemountingwhenpresentedeitherfloxp/floxp(ePet-Cre)intoLmx1bmice,leadingtotheabsenceofse-withachoiceofamaleandafemaletar

5、getoronlywithafemalerotonergicneuronsinthebrainwithoutaffecting5-HTinthe−/−target.Pharmacologicalmanipulationsandgeneticrescueexperi-periphery(27).WehaveobtainedfemaleLmx1bmicementsshowedthatserotoninisrequiredinadults.Behavioralandconfirmedthatthelevelsof5-HTanditsmetabolite5-changescausedbyd

6、eficientserotonergicsignalingwerenotduehydroxyindoleaceticacid(5-HIAA)werelowerinthebrainsof−/−tochangesinplasmaconcentrationsofsexhormones.Wedemon-homozygous(Lmx1b)mutantfemalesthanthoseintheWT+/++/−stratethatageneticmanipulationreversessexualpreferencewith-(Lmx1b)andheterozygous(Lmx1b)female

7、s(Fig.S1Aandoutinvolvingsexhormones.OurresultsindicatethatserotoninB).Thelevelof5-HTinheterozygousfemaleswasalsolowerthancontrolssexualpreference.thatintheWT.Sexualpreferencewasfirstinvestigatedbypresentingamaleandafemaletargetmousetoatestfema

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