{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T00:23:54Z","timestamp":1789691034781,"version":"4.0.1"},"reference-count":48,"publisher":"American Physiological Society","issue":"3","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American Journal of Physiology-Renal Physiology"],"published-print":{"date-parts":[[2006,9]]},"abstract":"<jats:p>In response to gestational high salt intake, BdkrB2\u2212\/\u2212 embryos acquire an aberrant renal phenotype mimicking renal dysplasia in humans. Genetic analysis identified p53 as a mediator of the renal dysplasia in salt-stressed BdkrB2\u2212\/\u2212 mice, acting partly via repression of terminal epithelial differentiation genes. The present study tested the hypothesis that inactivation of BdkrB2 predisposes the salt-stressed embryo to p53-mediated metanephric apoptosis. Newborn BdkrB2\u2212\/\u2212 pups exhibited hyperphosphorylation of metanephric p53 on serine 20 (mouse serine 23), a modification known to increase p53 stability and apoptotic activity. As a result, there was widespread, ectopic expression of p53 in the BdkrB2\u2212\/\u2212 kidney. However, no differences were found in the apoptosis index or gene expression in BdkrB2\u2212\/\u2212 and +\/+ kidneys, indicating that p53 stabilization as a result of BdkrB2 inactivation is not sufficient to induce metanephric apoptosis. On gestational salt stress, fulminant metanephric apoptosis and enhanced Bax gene expression occurred in BdkrB2\u2212\/\u2212 but not their +\/\u2212 or +\/+ littermates. Germline deletion of p53 from BdkrB2\u2212\/\u2212 mice prevented Bax activation and normalized the apoptosis index. Rescue of metanephric apoptosis in BdkrB2\u2212\/\u2212 mice was similarly achieved by Bax gene deletion. Aberrant apoptosis in salt-stressed BdkrB2\u2212\/\u2212 mice was triggered on embryonic day E15.5 and involved both ureteric bud (UB) and metanephric mesenchyme-derived nephron elements. Cultured E12.5 salt-stressed BdkrB2\u2212\/\u2212 metanephroi manifested stunted UB branching compared with +\/\u2212 and +\/+ littermates; the abnormal UB branching was corrected by p53 deletion. Our results suggest a model whereby a seemingly silent genetic mutation of BdkrB2 predisposes mice to renal dysplasia by creating a \u201cpreapoptotic\u201d state through p53 activation.<\/jats:p>","DOI":"10.1152\/ajprenal.00037.2006","type":"journal-article","created":{"date-parts":[[2006,3,30]],"date-time":"2006-03-30T01:12:34Z","timestamp":1143681154000},"page":"F670-F682","source":"Crossref","is-referenced-by-count":12,"title":["Susceptibility to metanephric apoptosis in bradykinin B2 receptor null mice via the p53-Bax pathway"],"prefix":"10.1152","volume":"291","author":[{"given":"Hao","family":"Fan","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jana","family":"Stefkova","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samir 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