Smar nductoof B catenprotewas also observed the AK nduced by renal schema reperfusonjury.To determne tubular segment specfcty of B catennductoAK, we employed double mmunostanng for B catenand varous tubular markers the kdneys right after folc acd njecton.As lustrated Fgure 1e, B catenprotewas apparently detectable all tubular segments, ncludng proxmal tubule, cortcal thck ascendng lmb, dstal tubule and collectng duct epthela AK soon after folc acd njecton.Mce wth tubule specfc ablatoof B catenare phenotypcally regular We sought to determne the potental part of endogenous B catennormal renal physology and regulatng tssue njury AK.To ths end, we created condtonal knockout mce whch B catengene s specfcally dsrupted renal tubules by utzng the Cre Loxsystem.homozygous B catenfloxed mce have been mated wth KsCre transgenc mce expressng Cre recombnase read the full info here underneath the handle of Kscadherpromoter.As showFgure 2, a and b, condtonal knockout mce wth tubule specfc ablatoof endogenous B catenwere produced.
Age and sex matched B catenfloxed mce from the very same ltters have been used as controls.To confrm condtonal ablatoof B catenn, we examned ts expressothe kdneys immediately after folc acd njecton, snce renal B catenwas nduced that settng.As showFgure 2c, Westerblot analyses of total kdney lysates revealed a marked reductoof renal B catenproteKsB cat mce, comparng wth the controls.mmunohstochemcal order Salubrinal stanng for B catenalso showed a tubule specfc reductoof B catenprotethe kdneys of KsB cat mce.Mce wth tubule specfc deletoof B catenwere phenotypcally ordinary.There was no apprecable abnormalty kdney morphology of KsB cat mce.KsB cat mce exhbted smar physique weghts since the controls.Kdney functon, as reflected by serum creatnne and urnary albumn, was ndstngushable betweeKsB cat mce as well as the controls.As B catens knowto bnd to E cadherand medates epthelal adherent nteracton, ths prompted us to nvestgate the reasowhy ablatoof ths protehas not resulted a defect at epthelal adherens junctons.
As showFgure 3e, co mmunoprecptatodemonstrates that B catenphyscally nteracted wth E cadherthe manage kdneys.As anticipated, ths nteractoof B catenE cadherwas reduced the kdneys of KsB cat mce.nterestngly, the nteractobetweeE cadherand catenn, yet another member within the catenfamy, was

markedly nduced KsB cat kdneys, compared to the controls.The protelevels of catenand E cadhern,however, have been not changed the KsB cat kdneys, ndcatng that the ncreased assocatoof E cadhercatens not due to ther upregulaton.These results suggest that the absence of B catenn, catenfunctonally substtutes for ts function mantanng the ntegrty of epthelal cell cell adherens junctons.Tubule specfc ablatoof B catenaggravates acute kdney njury We next examned the effects of B catenablatooacute tubular njury soon after folc acd njecton.Of nterest, nne out of eghteeKsB cat mce ded wth2 days after folc acd admnstraton, whereas only four out of seventeecontrol mce deceased precisely the same perod underneath the dentcal condtons.