{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T12:34:29Z","timestamp":1790253269903,"version":"4.1.0"},"reference-count":51,"publisher":"MDPI AG","issue":"21","license":[{"start":{"date-parts":[[2019,10,24]],"date-time":"2019-10-24T00:00:00Z","timestamp":1571875200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004837","name":"Ministerio de Ciencia e Innovaci\u00f3n","doi-asserted-by":"publisher","award":["SAF2015-64869-R-FEDER"],"award-info":[{"award-number":["SAF2015-64869-R-FEDER"]}],"id":[{"id":"10.13039\/501100004837","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004837","name":"Ministerio de Ciencia e Innovaci\u00f3n","doi-asserted-by":"publisher","award":["RTI2018-09211-B-100"],"award-info":[{"award-number":["RTI2018-09211-B-100"]}],"id":[{"id":"10.13039\/501100004837","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100008054","name":"Fundaci\u00f3n Ram\u00f3n Areces","doi-asserted-by":"publisher","award":["I.O.F.R.ARECES"],"award-info":[{"award-number":["I.O.F.R.ARECES"]}],"id":[{"id":"10.13039\/100008054","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002809","name":"Generalitat de Catalunya","doi-asserted-by":"publisher","award":["2017 SGR 961"],"award-info":[{"award-number":["2017 SGR 961"]}],"id":[{"id":"10.13039\/501100002809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Lysinuric protein intolerance (LPI) is a rare autosomal disease caused by defective cationic amino acid (CAA) transport due to mutations in SLC7A7, which encodes for the y+LAT1 transporter. LPI patients suffer from a wide variety of symptoms, which range from failure to thrive, hyperammonemia, and nephropathy to pulmonar alveolar proteinosis (PAP), a potentially life-threatening complication. Hyperammonemia is currently prevented by citrulline supplementation. However, the full impact of this treatment is not completely understood. In contrast, there is no defined therapy for the multiple reported complications of LPI, including PAP, for which bronchoalveolar lavages do not prevent progression of the disease. The lack of a viable LPI model prompted us to generate a tamoxifen-inducible Slc7a7 knockout mouse (Slc7a7\u2212\/\u2212). The Slc7a7\u2212\/\u2212 model resembles the human LPI phenotype, including malabsorption and impaired reabsorption of CAA, hypoargininemia and hyperammonemia. Interestingly, the Slc7a7\u2212\/\u2212 mice also develops PAP and neurological impairment. We observed that citrulline treatment improves the metabolic derangement and survival. On the basis of our findings, the Slc7a7\u2212\/\u2212 model emerges as a promising tool to further study the complexity of LPI, including its immune-like complications, and to design evidence-based therapies to halt its progression.<\/jats:p>","DOI":"10.3390\/ijms20215294","type":"journal-article","created":{"date-parts":[[2019,10,25]],"date-time":"2019-10-25T04:41:27Z","timestamp":1571978487000},"page":"5294","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":26,"title":["Inducible Slc7a7 Knockout Mouse Model Recapitulates Lysinuric Protein Intolerance Disease"],"prefix":"10.3390","volume":"20","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9261-4373","authenticated-orcid":false,"given":"Susanna","family":"Bodoy","sequence":"first","affiliation":[{"name":"Institute for Research in Biomedicine (IRB Barcelona), The Barcelona Institute of Science and Technology (BIST), 08028 Barcelona, Spain"},{"name":"Department of Biosciences, University of Vic, 08500 Vic, Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Enfermedades Raras (CIBERER), 08003 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fernando","family":"Sotillo","sequence":"additional","affiliation":[{"name":"Institute for Research in Biomedicine (IRB Barcelona), The Barcelona Institute of Science and Technology (BIST), 08028 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7211-3229","authenticated-orcid":false,"given":"Meritxell","family":"Espino-Guarch","sequence":"additional","affiliation":[{"name":"Sidra Medicine, Translational Medicine Department, Doha 26999, Qatar"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Pia","family":"Sperandeo","sequence":"additional","affiliation":[{"name":"Department of Translational Medicine, Section of Pediatrics, Federico II University of Naples, 80138 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aida","family":"Ormazabal","sequence":"additional","affiliation":[{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Enfermedades Raras (CIBERER), 08003 Barcelona, Spain"},{"name":"Department of Clinical Biochemistry, Hospital Sant Joan de D\u00e9u (HSJD), 08950 Esplugues del Llobregat, Spain"},{"name":"Institut de Recerca Sant Joan de D\u00e9u, 08950 Esplugues de Llobregat, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonio","family":"Zorzano","sequence":"additional","affiliation":[{"name":"Institute for Research in Biomedicine (IRB Barcelona), The Barcelona Institute of Science and Technology (BIST), 08028 Barcelona, Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Obesidad (CIBEROB), 28029 Madrid, Spain"},{"name":"Department of Biochemistry and Molecular Biomedicine, Faculty of Biology, University of Barcelona, 08028 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gianfranco","family":"Sebastio","sequence":"additional","affiliation":[{"name":"Department of Translational Medicine, Section of Pediatrics, Federico II University of Naples, 80138 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rafael","family":"Artuch","sequence":"additional","affiliation":[{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Enfermedades Raras (CIBERER), 08003 Barcelona, Spain"},{"name":"Department of Clinical Biochemistry, Hospital Sant Joan de D\u00e9u (HSJD), 08950 Esplugues del Llobregat, Spain"},{"name":"Institut de Recerca Sant Joan de D\u00e9u, 08950 Esplugues de Llobregat, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manuel","family":"Palac\u00edn","sequence":"additional","affiliation":[{"name":"Institute for Research in Biomedicine (IRB Barcelona), The Barcelona Institute of Science and Technology (BIST), 08028 Barcelona, Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Enfermedades Raras (CIBERER), 08003 Barcelona, Spain"},{"name":"Department of Biochemistry and Molecular Biomedicine, Faculty of Biology, University of Barcelona, 08028 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2019,10,24]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"293","DOI":"10.1038\/6809","article-title":"Identification of SLC7A7, encoding y+LAT-1, as the lysinuric protein intolerance gene","volume":"21","author":"Torrents","year":"1999","journal-title":"Nat. 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