Exploring the Contribution of the Transporter AGT1/rBAT in Cystinuria Progression: Insights from Mouse Models and a Retrospective Cohort Study

More than 20 years have passed since the identification of SLC3A1 and SLC7A9 as causative genes for cystinuria. However, cystinuria patients exhibit significant variability in the age of lithiasis onset, recurrence, and response to treatment, suggesting the presence of modulatory factors influencing...

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Autores: Gràcia-Garcia, Silvia, Mayayo Vallverdú, Clara, Prat, Esther, Vecino-Pérez, Marta, González, Laura, San Miguel, Luz, Lopera, Noelia, Arias, Ángela, Artuch, Rafael, López de Heredia, Miguel, Torrecilla, Carlos, Rousaud-Barón, Ferran, Angerri, Oriol, Errasti-Murugarren, Ekaitz, Nunes Martínez, Virginia
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2023
País:España
Institución:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
Repositorio:Recercat. Dipósit de la Recerca de Catalunya
OAI Identifier:oai:recercat.cat:2445/208552
Acceso en línea:https://hdl.handle.net/2445/208552
Access Level:acceso abierto
Palabra clave:Cistinúria
Ronyó
Càlculs renals
Cystinuria
Kidney
Kidney calculi
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spelling Exploring the Contribution of the Transporter AGT1/rBAT in Cystinuria Progression: Insights from Mouse Models and a Retrospective Cohort StudyGràcia-Garcia, SilviaMayayo Vallverdú, ClaraPrat, EstherVecino-Pérez, MartaGonzález, LauraSan Miguel, LuzLopera, NoeliaArias, ÁngelaArtuch, RafaelLópez de Heredia, MiguelTorrecilla, CarlosRousaud-Barón, FerranAngerri, OriolErrasti-Murugarren, EkaitzNunes Martínez, VirginiaCistinúriaRonyóCàlculs renalsCystinuriaKidneyKidney calculiMore than 20 years have passed since the identification of SLC3A1 and SLC7A9 as causative genes for cystinuria. However, cystinuria patients exhibit significant variability in the age of lithiasis onset, recurrence, and response to treatment, suggesting the presence of modulatory factors influencing cystinuria severity. In 2016, a second renal cystine transporter, AGT1, encoded by the SLC7A13 gene, was discovered. Although it was discarded as a causative gene for cystinuria, its possible effect as a modulatory gene remains unexplored. Thus, we analyzed its function in mouse models of cystinuria, screened the SLC7A13 gene in 34 patients with different lithiasic phenotypes, and functionally characterized the identified variants. Mice results showed that AGT1/rBAT may have a protective role against cystine lithiasis. In addition, among the four missense variants detected in patients, two exhibited a 25% impairment in AGT1/rBAT transport. However, no correlation between SLC7A13 genotypes and lithiasis phenotypes was observed in patients, probably because these variants were found in heterozygous states. In conclusion, our results, consistent with a previous study, suggest that AGT1/rBAT does not have a relevant effect on cystinuria patients, although an impact in patients carrying homozygous pathogenic variants cannot be discarded.MDPI2024202420232024info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersion12 p.application/pdfhttps://hdl.handle.net/2445/208552Articles publicats en revistes (Ciències Fisiològiques)reponame:Recercat. Dipósit de la Recerca de Catalunyainstname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)InglésReproducció del document publicat a: https://doi.org/10.3390/ijms242417140International Journal of Molecular Sciences, 2023, vol. 24, num.24https://doi.org/10.3390/ijms242417140cc-by (c) Mayayo-Vallverdú, C. et al., 2023http://creativecommons.org/licenses/by/4.0/info:eu-repo/semantics/openAccessoai:recercat.cat:2445/2085522026-05-29T05:05:01Z
dc.title.none.fl_str_mv Exploring the Contribution of the Transporter AGT1/rBAT in Cystinuria Progression: Insights from Mouse Models and a Retrospective Cohort Study
title Exploring the Contribution of the Transporter AGT1/rBAT in Cystinuria Progression: Insights from Mouse Models and a Retrospective Cohort Study
spellingShingle Exploring the Contribution of the Transporter AGT1/rBAT in Cystinuria Progression: Insights from Mouse Models and a Retrospective Cohort Study
Gràcia-Garcia, Silvia
Cistinúria
Ronyó
Càlculs renals
Cystinuria
Kidney
Kidney calculi
title_short Exploring the Contribution of the Transporter AGT1/rBAT in Cystinuria Progression: Insights from Mouse Models and a Retrospective Cohort Study
title_full Exploring the Contribution of the Transporter AGT1/rBAT in Cystinuria Progression: Insights from Mouse Models and a Retrospective Cohort Study
title_fullStr Exploring the Contribution of the Transporter AGT1/rBAT in Cystinuria Progression: Insights from Mouse Models and a Retrospective Cohort Study
title_full_unstemmed Exploring the Contribution of the Transporter AGT1/rBAT in Cystinuria Progression: Insights from Mouse Models and a Retrospective Cohort Study
title_sort Exploring the Contribution of the Transporter AGT1/rBAT in Cystinuria Progression: Insights from Mouse Models and a Retrospective Cohort Study
dc.creator.none.fl_str_mv Gràcia-Garcia, Silvia
Mayayo Vallverdú, Clara
Prat, Esther
Vecino-Pérez, Marta
González, Laura
San Miguel, Luz
Lopera, Noelia
Arias, Ángela
Artuch, Rafael
López de Heredia, Miguel
Torrecilla, Carlos
Rousaud-Barón, Ferran
Angerri, Oriol
Errasti-Murugarren, Ekaitz
Nunes Martínez, Virginia
author Gràcia-Garcia, Silvia
author_facet Gràcia-Garcia, Silvia
Mayayo Vallverdú, Clara
Prat, Esther
Vecino-Pérez, Marta
González, Laura
San Miguel, Luz
Lopera, Noelia
Arias, Ángela
Artuch, Rafael
López de Heredia, Miguel
Torrecilla, Carlos
Rousaud-Barón, Ferran
Angerri, Oriol
Errasti-Murugarren, Ekaitz
Nunes Martínez, Virginia
author_role author
author2 Mayayo Vallverdú, Clara
Prat, Esther
Vecino-Pérez, Marta
González, Laura
San Miguel, Luz
Lopera, Noelia
Arias, Ángela
Artuch, Rafael
López de Heredia, Miguel
Torrecilla, Carlos
Rousaud-Barón, Ferran
Angerri, Oriol
Errasti-Murugarren, Ekaitz
Nunes Martínez, Virginia
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Cistinúria
Ronyó
Càlculs renals
Cystinuria
Kidney
Kidney calculi
topic Cistinúria
Ronyó
Càlculs renals
Cystinuria
Kidney
Kidney calculi
description More than 20 years have passed since the identification of SLC3A1 and SLC7A9 as causative genes for cystinuria. However, cystinuria patients exhibit significant variability in the age of lithiasis onset, recurrence, and response to treatment, suggesting the presence of modulatory factors influencing cystinuria severity. In 2016, a second renal cystine transporter, AGT1, encoded by the SLC7A13 gene, was discovered. Although it was discarded as a causative gene for cystinuria, its possible effect as a modulatory gene remains unexplored. Thus, we analyzed its function in mouse models of cystinuria, screened the SLC7A13 gene in 34 patients with different lithiasic phenotypes, and functionally characterized the identified variants. Mice results showed that AGT1/rBAT may have a protective role against cystine lithiasis. In addition, among the four missense variants detected in patients, two exhibited a 25% impairment in AGT1/rBAT transport. However, no correlation between SLC7A13 genotypes and lithiasis phenotypes was observed in patients, probably because these variants were found in heterozygous states. In conclusion, our results, consistent with a previous study, suggest that AGT1/rBAT does not have a relevant effect on cystinuria patients, although an impact in patients carrying homozygous pathogenic variants cannot be discarded.
publishDate 2023
dc.date.none.fl_str_mv 2023
2024
2024
2024
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv https://hdl.handle.net/2445/208552
url https://hdl.handle.net/2445/208552
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv Reproducció del document publicat a: https://doi.org/10.3390/ijms242417140
International Journal of Molecular Sciences, 2023, vol. 24, num.24
https://doi.org/10.3390/ijms242417140
dc.rights.none.fl_str_mv cc-by (c) Mayayo-Vallverdú, C. et al., 2023
http://creativecommons.org/licenses/by/4.0/
info:eu-repo/semantics/openAccess
rights_invalid_str_mv cc-by (c) Mayayo-Vallverdú, C. et al., 2023
http://creativecommons.org/licenses/by/4.0/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv 12 p.
application/pdf
dc.publisher.none.fl_str_mv MDPI
publisher.none.fl_str_mv MDPI
dc.source.none.fl_str_mv Articles publicats en revistes (Ciències Fisiològiques)
reponame:Recercat. Dipósit de la Recerca de Catalunya
instname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
instname_str Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
reponame_str Recercat. Dipósit de la Recerca de Catalunya
collection Recercat. Dipósit de la Recerca de Catalunya
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15,812429

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