{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,7]],"date-time":"2026-08-07T19:57:15Z","timestamp":1786132635569,"version":"build-2736575974"},"reference-count":30,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"8","funder":[{"DOI":"10.13039\/501100003329","name":"Ministerio de Econom\u00eda y Competitividad","doi-asserted-by":"publisher","award":["BFU2010-47175-P"],"award-info":[{"award-number":["BFU2010-47175-P"]}],"id":[{"id":"10.13039\/501100003329","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003329","name":"Ministerio de Econom\u00eda y Competitividad","doi-asserted-by":"publisher","award":["BFU2017-83646-P"],"award-info":[{"award-number":["BFU2017-83646-P"]}],"id":[{"id":"10.13039\/501100003329","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003030","name":"Ag\u00e8ncia de Gesti\u00f3 d\u2019Ajuts Universitaris i de Recerca","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100003030","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Universitat de Lleida"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JASN"],"published-print":{"date-parts":[[2019,8]]},"abstract":"<jats:sec>\n                    <jats:title>Significance Statement<\/jats:title>\n                    <jats:p>Sprouty1 is a critical regulator of genitourinary development that ensures only one kidney forms on each side of the embryo. The molecular mechanisms that Sprouty1 uses to do this are largely unknown. The authors show that removing a single tyrosine from Sprouty1 in mice is enough to inactivate its function during genitourinary development. Knockin mice lacking this tyrosine develop supernumerary kidneys, megaureter, and vesicoureteral reflux, the same defects seen in Sprouty1 knockout mice. These findings shed light on the elusive mechanisms of action of Sprouty proteins and provide a valuable tool to investigate the developmental origin of human congenital anomalies of kidney and lower urinary tract.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      Studies in mice suggest that perturbations of the GDNF-Ret signaling pathway are a major genetic cause of congenital anomalies of the kidney and urinary tract (CAKUT). Mutations in Sprouty1, an intracellular Ret inhibitor, results in supernumerary kidneys, megaureters, and hydronephrosis in mice. But the underlying molecular mechanisms involved and which structural domains are essential for Sprouty1 function are a matter of controversy, partly because studies have so far relied on ectopic overexpression of the gene in cell lines. A conserved N-terminal tyrosine has been frequently, but not always, identified as critical for the function of Sprouty1\n                      <jats:italic toggle=\"yes\">in vitro<\/jats:italic>\n                      .\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      We generated Sprouty1 knockin mice bearing a tyrosine-to-alanine substitution in position 53, corresponding to the conserved N-terminal tyrosine of Sprouty1. We characterized the development of the genitourinary systems in these mice\n                      <jats:italic toggle=\"yes\">via<\/jats:italic>\n                      different methods, including the use of reporter mice expressing EGFP from the Ret locus, and whole-mount cytokeratin staining.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Mice lacking this tyrosine grow ectopic ureteric buds that will ultimately form supernumerary kidneys, a phenotype indistinguishable to that of Sprouty1 knockout mice. Sprouty1 knockin mice also present megaureters and vesicoureteral reflux, caused by failure of ureters to separate from Wolffian ducts and migrate to their definitive position.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Tyrosine 53 is absolutely necessary for Sprouty1 function during genitourinary development in mice.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1681\/asn.2018111085","type":"journal-article","created":{"date-parts":[[2019,7,12]],"date-time":"2019-07-12T15:25:14Z","timestamp":1562945114000},"page":"1398-1411","source":"Crossref","is-referenced-by-count":6,"title":["Sprouty1 Controls Genitourinary Development via its N-Terminal Tyrosine"],"prefix":"10.1681","volume":"30","author":[{"given":"Marta","family":"Vaquero","sequence":"first","affiliation":[{"name":"Experimental Medicine and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara","family":"Cuesta","sequence":"additional","affiliation":[{"name":"Experimental Medicine and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carlos","family":"Anerillas","sequence":"additional","affiliation":[{"name":"Experimental Medicine and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gisela","family":"Alt\u00e9s","sequence":"additional","affiliation":[{"name":"Experimental Medicine and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joan","family":"Ribera","sequence":"additional","affiliation":[{"name":"Experimental Medicine and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M. Albert","family":"Basson","sequence":"additional","affiliation":[{"name":"Centre for Craniofacial and Regenerative Biology, King\u2019s College London, Guy\u2019s Hospital, London, UK; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonathan D.","family":"Licht","sequence":"additional","affiliation":[{"name":"The University of Florida Health Cancer Center, The University of Florida Cancer\/Genetics Research Complex, Gainesville, Florida"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joaquim","family":"Egea","sequence":"additional","affiliation":[{"name":"Basic Medical Sciences, Universitat de Lleida\/Institut de Recerca Biom\u00e8dica de Lleida, Lleida, Spain;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mario","family":"Encinas","sequence":"additional","affiliation":[{"name":"Experimental Medicine and"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","published-online":{"date-parts":[[2019,7,12]]},"reference":[{"key":"B1-20231016","doi-asserted-by":"crossref","first-page":"791","DOI":"10.1038\/nrg2205","article-title":"Renal abnormalities and their developmental origin.","volume":"8","author":"Schedl","year":"2007","journal-title":"Nat Rev Genet"},{"key":"B2-20231016","doi-asserted-by":"crossref","first-page":"597","DOI":"10.1007\/s00467-013-2606-5","article-title":"To bud or not to bud: The RET perspective in CAKUT.","volume":"29","author":"Davis","year":"2014","journal-title":"Pediatr Nephrol"},{"key":"B3-20231016","doi-asserted-by":"crossref","first-page":"1082","DOI":"10.1038\/ng1645","article-title":"Apoptosis induced by vitamin A signaling is crucial for connecting the ureters to the bladder.","volume":"37","author":"Batourina","year":"2005","journal-title":"Nat Genet"},{"key":"B4-20231016","first-page":"924","article-title":"Maturation of 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