{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T12:58:24Z","timestamp":1791291504508,"version":"4.3.0"},"reference-count":46,"publisher":"American Physiological Society","issue":"12","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American Journal of Physiology-Renal Physiology"],"published-print":{"date-parts":[[2013,12,15]]},"abstract":"<jats:p>\n                    Cystinuria is an autosomal recessive disease caused by mutations in SLC3A1 ( rBAT) and SLC7A9 ( b\n                    <jats:sup>0,+<\/jats:sup>\n                    AT). Gene targeting of the catalytic subunit ( Slc7a9) in mice leads to excessive excretion of cystine, lysine, arginine, and ornithine. Here, we studied this non-type I cystinuria mouse model using gene expression analysis, Western blotting, clearance, and brush-border membrane vesicle (BBMV) uptake experiments to further characterize the renal and intestinal consequences of losing Slc7a9 function. The electrogenic and BBMV flux studies in the intestine suggested that arginine and ornithine are transported via other routes apart from system b\n                    <jats:sup>0,+<\/jats:sup>\n                    . No remarkable gene expression changes were observed in other amino acid transporters and the peptide transporters in the intestine and kidney. Furthermore, the glomerular filtration rate (GFR) was reduced by 30% in knockout animals compared with wild-type animals. The fractional excretion of arginine was increased as expected (\u223c100%), but fractional excretions of lysine (\u223c35%), ornithine (\u223c16%), and cystine (\u223c11%) were less affected. Loss of function of b\n                    <jats:sup>0,+<\/jats:sup>\n                    AT reduced transport of cystine and arginine in renal BBMVs and completely abolished the exchanger activity of dibasic amino acids with neutral amino acids. In conclusion, loss of Slc7a9 function decreases the GFR and increases the excretion of several amino acids to a lesser extent than expected with no clear regulation at the mRNA and protein level of alternative transporters and no increased renal epithelial uptake. These observations indicate that transporters located in distal segments of the kidney and\/or metabolic pathways may partially compensate for Slc7a9 loss of function.\n                  <\/jats:p>","DOI":"10.1152\/ajprenal.00221.2013","type":"journal-article","created":{"date-parts":[[2013,10,10]],"date-time":"2013-10-10T12:01:17Z","timestamp":1381406477000},"page":"F1645-F1655","source":"Crossref","is-referenced-by-count":23,"title":["Differential cystine and dibasic amino acid handling after loss of function of the amino acid transporter b\n                    <sup>0,+<\/sup>\n                    AT (Slc7a9) in mice"],"prefix":"10.1152","volume":"305","author":[{"given":"Andrea Di","family":"Giacopo","sequence":"first","affiliation":[{"name":"Institute of Physiology-Z\u00fcrich Center for Integrative Human Physiology (ZIHP), University of Z\u00fcrich, Z\u00fcrich, Switzerland;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isabel","family":"Rubio-Aliaga","sequence":"additional","affiliation":[{"name":"Institute of Physiology-Z\u00fcrich Center for Integrative Human Physiology (ZIHP), University of Z\u00fcrich, Z\u00fcrich, Switzerland;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessandra","family":"Cantone","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Chair of Nephrology, Second University of Naples, Naples, Italy;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ferruh","family":"Artunc","sequence":"additional","affiliation":[{"name":"Department of Physiology, University of T\u00fcbingen, T\u00fcbingen, Germany;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rexhep","family":"Rexhepaj","sequence":"additional","affiliation":[{"name":"Department of Physiology, University of T\u00fcbingen, T\u00fcbingen, Germany;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isabelle","family":"Frey-Wagner","sequence":"additional","affiliation":[{"name":"Molecular Nutrition Unit, Technical University of Munich, Freising, Germany;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mariona","family":"Font-Llitj\u00f3s","sequence":"additional","affiliation":[{"name":"Medical and Molecular Genetics Center, Institut d'Investigaci\u00f3 Biom\u00e8dica de Bellvitge (IDIBELL), L'Hospitalet de Llobregat, Spain;"},{"name":"U730 CIBERER, Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicole","family":"Gehring","sequence":"additional","affiliation":[{"name":"Institute of Physiology-Z\u00fcrich Center for Integrative Human Physiology (ZIHP), University of Z\u00fcrich, Z\u00fcrich, Switzerland;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gerti","family":"Stange","sequence":"additional","affiliation":[{"name":"Institute of Physiology-Z\u00fcrich Center for Integrative Human Physiology (ZIHP), University of Z\u00fcrich, Z\u00fcrich, Switzerland;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isabel","family":"Jaenecke","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, University Medical Center of the Johannes Gutenberg University, Mainz, Germany;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nilufar","family":"Mohebbi","sequence":"additional","affiliation":[{"name":"Institute of Physiology-Z\u00fcrich Center for Integrative Human Physiology (ZIHP), University of Z\u00fcrich, Z\u00fcrich, Switzerland;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ellen I.","family":"Closs","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, University Medical Center of the Johannes Gutenberg University, Mainz, Germany;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manuel","family":"Palac\u00edn","sequence":"additional","affiliation":[{"name":"IRB Barcelona, Department of Biochemistry and Molecular Biology, University of Barcelona and U731 CIBERER, Barcelona, Spain;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Virginia","family":"Nunes","sequence":"additional","affiliation":[{"name":"Medical and Molecular Genetics Center, Institut d'Investigaci\u00f3 Biom\u00e8dica de Bellvitge (IDIBELL), L'Hospitalet de Llobregat, Spain;"},{"name":"Department of Physiological Sciences II, University of Barcelona, Spain; and"},{"name":"U730 CIBERER, Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hannelore","family":"Daniel","sequence":"additional","affiliation":[{"name":"Molecular Nutrition Unit, Technical University of Munich, Freising, Germany;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Florian","family":"Lang","sequence":"additional","affiliation":[{"name":"Department of Physiology, University of T\u00fcbingen, T\u00fcbingen, Germany;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giovambattista","family":"Capasso","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Chair of Nephrology, Second University of Naples, Naples, Italy;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carsten A.","family":"Wagner","sequence":"additional","affiliation":[{"name":"Institute of Physiology-Z\u00fcrich Center for Integrative Human Physiology (ZIHP), University of Z\u00fcrich, Z\u00fcrich, Switzerland;"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"24","reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mam.2008.08.004"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1007\/BF01063939"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M111.241323"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1007\/s00424-002-0840-y"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.00018.2006"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1042\/BJ20101912"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1038\/sj.ki.5002790"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1038\/ng.566"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.271.30.17761"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1038\/nrneph.2010.69"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1007\/s00232-006-0875-7"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.physiol.66.032102.144149"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.00123.2002"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.1993.265.6.F830"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2004.065037"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1152\/ajplung.1989.257.4.L163"},{"key":"B17","first-page":"467","volume":"56","author":"de Sanctis L","year":"2001","journal-title":"Clin Nephrol"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddg228"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.00121.2007"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1016\/0026-0495(80)90098-0"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1016\/j.mam.2012.10.007"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1152\/physiolgenomics.00193.2006"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.00061.2002"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1038\/ng1405"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1038\/ng.568"},{"key":"B26","author":"Kuhn MW","year":"2011","journal-title":"Contrast: a Collection of Contrast Methods (Online)"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1042\/bj1940443"},{"key":"B28","author":"Morales M","year":"2012","journal-title":"Sciplot: Scientific Graphing Functions for Factorial Designs (Online)"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1152\/ajpgi.00017.2011"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1007\/s00424-003-1062-7"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1152\/physiol.00051.2004"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1101\/gad.11.7.914"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddg189"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.1091\/mbc.10.12.4135"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.1042\/bj20030956"},{"key":"B36","author":"Pinheiro JB, D","year":"2013","journal-title":"Nlme: Linear and Nonlinear Mixed Effects Models (Online)"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.1096\/fj.05-5676com"},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.1080\/00498250701875254"},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.1007\/978-0-387-75969-2"},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.1038\/ng1406"},{"key":"B41","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.1999.276.5.F658"},{"key":"B42","author":"Team RC.","journal-title":"R: A language and environment for statistical computing"},{"key":"B43","doi-asserted-by":"publisher","DOI":"10.1038\/6809"},{"key":"B44","doi-asserted-by":"publisher","DOI":"10.1021\/bi011345c"},{"key":"B45","doi-asserted-by":"publisher","DOI":"10.1007\/s00424-003-1086-z"},{"key":"B46","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.2001.281.4.C1077"}],"container-title":["American Journal of Physiology-Renal Physiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.physiology.org\/doi\/pdf\/10.1152\/ajprenal.00221.2013","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2019,9,8]],"date-time":"2019-09-08T19:47:57Z","timestamp":1567972077000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.physiology.org\/doi\/10.1152\/ajprenal.00221.2013"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2013,12,15]]},"references-count":46,"journal-issue":{"issue":"12","published-print":{"date-parts":[[2013,12,15]]}},"alternative-id":["10.1152\/ajprenal.00221.2013"],"URL":"https:\/\/doi.org\/10.1152\/ajprenal.00221.2013","relation":{},"ISSN":["1931-857X","1522-1466"],"issn-type":[{"value":"1931-857X","type":"print"},{"value":"1522-1466","type":"electronic"}],"subject":[],"published":{"date-parts":[[2013,12,15]]}}}