{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,18]],"date-time":"2026-10-18T02:16:20Z","timestamp":1792289780470,"version":"4.4.0"},"reference-count":17,"publisher":"Springer Science and Business Media LLC","issue":"7","license":[{"start":{"date-parts":[[2024,1,29]],"date-time":"2024-01-29T00:00:00Z","timestamp":1706486400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2024,1,29]],"date-time":"2024-01-29T00:00:00Z","timestamp":1706486400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Pediatr Res"],"published-print":{"date-parts":[[2024,6]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec>\n                <jats:title>Background<\/jats:title>\n                <jats:p>The prorenin receptor (PRR) plays a critical role in ureteric bud (UB) branching morphogenesis. DOT1 Like (DOT1L), a histone methyltransferase specific for Histone 3 lysine 79 (H3K79), is important for differentiation of the UB-derived renal collecting duct cells. In this study, we tested whether DOT1L\/H3 dimethyl K79 (H3m2K79) are regulated by <jats:italic>PRR<\/jats:italic> deletion in the UB and UB-derived collecting ducts in the embryonic mouse kidneys.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Methods<\/jats:title>\n                <jats:p>Mutant <jats:italic>Hoxb7<\/jats:italic><jats:sup>Cre+<\/jats:sup>\/<jats:italic>PRR<\/jats:italic><jats:sup>flox\/flox<\/jats:sup> (<jats:italic>PRR<\/jats:italic><jats:sup>UB<jats:italic>-\/-<\/jats:italic><\/jats:sup>) and control <jats:italic>PRR<\/jats:italic><jats:sup>UB+\/+<\/jats:sup>, mice were studied on embryonic (E) day E17.5. DOT1L mRNA and protein expression in the kidney was examined by real-time qRT-PCR and immunohistochemistry, respectively. H3m2K79 protein expression was determined by immunohistochemistry and Western blot analysis.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p><jats:italic>DOT1L<\/jats:italic> mRNA levels were decreased in mutant compared to control mice (0.68\u2009\u00b1\u20090.06 vs. 1.0\u2009\u00b1\u20090.01, <jats:italic>p<\/jats:italic>\u2009&lt;\u20090.01). DOT1L and H3m2K79 immunostaining was reduced in the mutant vs. control kidneys (Dot1: 0.62\u2009\u00b1\u20090.03 vs. 1.0\u2009\u00b1\u20090.01, <jats:italic>p<\/jats:italic>\u2009&lt;\u20090.05; H3m2K79: 0.64\u2009\u00b1\u20090.04 vs.1.1\u2009\u00b1\u20090.01. <jats:italic>p<\/jats:italic>\u2009&lt;\u20090.05.). Western blot analysis revealed decreased H3m2K79 protein levels in mutant compared to control kidneys (1.0\u2009\u00b1\u20090.06 vs. 1.5\u2009\u00b1\u20090.02, <jats:italic>p<\/jats:italic>\u2009&lt;\u20090.05).<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusion<\/jats:title>\n                <jats:p>Targeted deletion of the <jats:italic>PRR<\/jats:italic> in the UB and UB-derived collecting ducts results in reduced <jats:italic>DOT1L<\/jats:italic> gene\/protein and H3m2K79 protein expression in the embryonic mouse metanephroi in vivo.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Impact<\/jats:title>\n                <jats:p><jats:list list-type=\"bullet\">\n                  <jats:list-item>\n                    <jats:p>The role of histone methylation in mediating the effect of the prorenin receptor on the ureteric bud branching (UB) morphogenesis and urine acidification during kidney development is unknown.<\/jats:p>\n                  <\/jats:list-item>\n                  <jats:list-item>\n                    <jats:p>We demonstrate that histone H3 lysine (K) 79 dimethylation by methyltransferase Dot1 is reduced in the embryonic kidney of mice that lack the prorenin receptor in the UB lineage.<\/jats:p>\n                  <\/jats:list-item>\n                <\/jats:list><\/jats:p>\n              <\/jats:sec>","DOI":"10.1038\/s41390-024-03026-5","type":"journal-article","created":{"date-parts":[[2024,1,29]],"date-time":"2024-01-29T08:02:24Z","timestamp":1706515344000},"page":"1754-1757","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Deletion of the prorenin receptor in the ureteric bud in mice inhibits Dot1\/H3K79 pathway"],"prefix":"10.1038","volume":"95","author":[{"given":"Renfang","family":"Song","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ihor V.","family":"Yosypiv","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,1,29]]},"reference":[{"key":"3026_CR1","doi-asserted-by":"publisher","first-page":"698","DOI":"10.1016\/j.devcel.2010.04.008","volume":"18","author":"F Costantini","year":"2010","unstructured":"Costantini, F. & Kopan, R. Patterning a complex organ: branching morphogenesis and nephron segmentation in kidney development. Dev. Cell 18, 698\u2013712 (2010).","journal-title":"Dev. Cell"},{"key":"3026_CR2","doi-asserted-by":"publisher","first-page":"353","DOI":"10.1007\/s00467-010-1629-4","volume":"26","author":"R Song","year":"2011","unstructured":"Song, R. & Yosypiv, I. V. Genetics of congenital anomalies of the kidney and urinary tract. Pediatr. Nephrol. 26, 353\u2013364 (2011).","journal-title":"Pediatr. Nephrol."},{"key":"3026_CR3","doi-asserted-by":"publisher","first-page":"e382","DOI":"10.1542\/peds.111.4.e382","volume":"111","author":"G Ardissino","year":"2003","unstructured":"Ardissino, G. et al. Epidemiology of chronic renal failure in children: Data From the ItalKid project. 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The (Pro)renin receptor site-specific and functional linkage to the vacuolar H+-ATPase in the kidney. Hypertension 54, 261\u2013269 (2009).","journal-title":"Hypertension"},{"key":"3026_CR7","first-page":"2823","volume":"5","author":"M Wong","year":"2015","unstructured":"Wong, M., Polly, P. & Liu, T. The histone methyltransferase DOT1L: regulatory functions and a cancer therapy target. Am. J. Cancer Res. 5, 2823\u20132837 (2015).","journal-title":"Am. J. Cancer Res."},{"key":"3026_CR8","doi-asserted-by":"publisher","first-page":"1235","DOI":"10.1080\/15592294.2020.1861168","volume":"16","author":"F Wang","year":"2021","unstructured":"Wang, F. et al. Targeted disruption of the histone lysine 79 methyltransferase Dot1L in nephron progenitors causes congenital renal dysplasia. 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