Digenic inheritance in cystinuria mouse model
Cystinuria is an aminoaciduria caused by mutations in the genes that encode the two subunits of the amino acid transport system b0,+, responsible for the renal reabsorption of cystine and dibasic amino acids. The clinical symptoms of cystinuria relate to nephrolithiasis, due to the precipitation of...
| Autores: | , , , , , , , |
|---|---|
| Tipo de documento: | artigo |
| Estado: | Versão publicada |
| Data de publicação: | 2015 |
| País: | España |
| Recursos: | Universidad de Barcelona |
| Repositório: | Dipòsit Digital de la UB |
| OAI Identifier: | oai:diposit.ub.edu:2445/99860 |
| Acesso em linha: | https://hdl.handle.net/2445/99860 |
| Access Level: | Acceso aberto |
| Palavra-chave: | Anàlisi d'aminoàcids Malalties del ronyó Càlculs renals Malalties hereditàries Fenotip Ratolins (Animals de laboratori) Cistinúria Amino acids analysis Kidney diseases Kidney calculi Genetic diseases Phenotype Mice (Laboratory animals) Cystinuria |
| id |
ES_b6bb0c5cbc25320ccc2d619536bfdca6 |
|---|---|
| oai_identifier_str |
oai:diposit.ub.edu:2445/99860 |
| network_acronym_str |
ES |
| network_name_str |
España |
| repository_id_str |
|
| spelling |
Digenic inheritance in cystinuria mouse modelEspino Gaurch, MeritxellFont i Llitjós, MarionaVilches, ClaraSalido, EduardoPrat, EstherLópez de Heredia, MiguelPalacín Prieto, ManuelNunes Martínez, VirginiaAnàlisi d'aminoàcidsMalalties del ronyóCàlculs renalsMalalties hereditàriesFenotipRatolins (Animals de laboratori)CistinúriaAmino acids analysisKidney diseasesKidney calculiGenetic diseasesPhenotypeMice (Laboratory animals)CystinuriaCystinuria is an aminoaciduria caused by mutations in the genes that encode the two subunits of the amino acid transport system b0,+, responsible for the renal reabsorption of cystine and dibasic amino acids. The clinical symptoms of cystinuria relate to nephrolithiasis, due to the precipitation of cystine in urine. Mutations in SLC3A1, which codes for the heavy subunit rBAT, cause cystinuria type A, whereas mutations in SLC7A9, which encodes the light subunit b0,+AT, cause cystinuria type B. By crossing Slc3a1-/- with Slc7a9-/- mice we generated a type AB cystinuria mouse model to test digenic inheritance of cystinuria. The 9 genotypes obtained have been analyzed at early (2- and 5-months) and late stage (8-months) of the disease. Monitoring the lithiasic phenotype by X-ray, urine amino acid content analysis and protein expression studies have shown that double heterozygous mice (Slc7a9+/-Slc3a1+/-) present lower expression of system b0,+ and higher hyperexcretion of cystine than single heterozygotes (Slc7a9+/-Slc3a1+/+ and Slc7a9+/+Slc3a1+/-) and give rise to lithiasis in 4% of the mice, demonstrating that cystinuria has a digenic inheritance in this mouse model. Moreover in this study it has been demonstrated a genotype/phenotype correlation in type AB cystinuria mouse model providing new insights for further molecular and genetic studies of cystinuria patients.Public Library of Science (PLoS)2015info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionapplication/pdfhttps://hdl.handle.net/2445/99860Articles publicats en revistes (Ciències Fisiològiques)reponame:Dipòsit Digital de la UBinstname:Universidad de BarcelonaInglésReproducció del document publicat a: http://dx.doi.org/10.1371/journal.pone.0137277PLoS One, 2015, vol. 10, num. 9, p. e0137277http://dx.doi.org/10.1371/journal.pone.0137277cc-by (c) Espino, Meritxell et al., 2015http://creativecommons.org/licenses/by/3.0/esinfo:eu-repo/semantics/openAccessoai:diposit.ub.edu:2445/998602026-05-27T06:46:51Z |
| dc.title.none.fl_str_mv |
Digenic inheritance in cystinuria mouse model |
| title |
Digenic inheritance in cystinuria mouse model |
| spellingShingle |
Digenic inheritance in cystinuria mouse model Espino Gaurch, Meritxell Anàlisi d'aminoàcids Malalties del ronyó Càlculs renals Malalties hereditàries Fenotip Ratolins (Animals de laboratori) Cistinúria Amino acids analysis Kidney diseases Kidney calculi Genetic diseases Phenotype Mice (Laboratory animals) Cystinuria |
| title_short |
Digenic inheritance in cystinuria mouse model |
| title_full |
Digenic inheritance in cystinuria mouse model |
| title_fullStr |
Digenic inheritance in cystinuria mouse model |
| title_full_unstemmed |
Digenic inheritance in cystinuria mouse model |
| title_sort |
Digenic inheritance in cystinuria mouse model |
| dc.creator.none.fl_str_mv |
Espino Gaurch, Meritxell Font i Llitjós, Mariona Vilches, Clara Salido, Eduardo Prat, Esther López de Heredia, Miguel Palacín Prieto, Manuel Nunes Martínez, Virginia |
| author |
Espino Gaurch, Meritxell |
| author_facet |
Espino Gaurch, Meritxell Font i Llitjós, Mariona Vilches, Clara Salido, Eduardo Prat, Esther López de Heredia, Miguel Palacín Prieto, Manuel Nunes Martínez, Virginia |
| author_role |
author |
| author2 |
Font i Llitjós, Mariona Vilches, Clara Salido, Eduardo Prat, Esther López de Heredia, Miguel Palacín Prieto, Manuel Nunes Martínez, Virginia |
| author2_role |
author author author author author author author |
| dc.subject.none.fl_str_mv |
Anàlisi d'aminoàcids Malalties del ronyó Càlculs renals Malalties hereditàries Fenotip Ratolins (Animals de laboratori) Cistinúria Amino acids analysis Kidney diseases Kidney calculi Genetic diseases Phenotype Mice (Laboratory animals) Cystinuria |
| topic |
Anàlisi d'aminoàcids Malalties del ronyó Càlculs renals Malalties hereditàries Fenotip Ratolins (Animals de laboratori) Cistinúria Amino acids analysis Kidney diseases Kidney calculi Genetic diseases Phenotype Mice (Laboratory animals) Cystinuria |
| description |
Cystinuria is an aminoaciduria caused by mutations in the genes that encode the two subunits of the amino acid transport system b0,+, responsible for the renal reabsorption of cystine and dibasic amino acids. The clinical symptoms of cystinuria relate to nephrolithiasis, due to the precipitation of cystine in urine. Mutations in SLC3A1, which codes for the heavy subunit rBAT, cause cystinuria type A, whereas mutations in SLC7A9, which encodes the light subunit b0,+AT, cause cystinuria type B. By crossing Slc3a1-/- with Slc7a9-/- mice we generated a type AB cystinuria mouse model to test digenic inheritance of cystinuria. The 9 genotypes obtained have been analyzed at early (2- and 5-months) and late stage (8-months) of the disease. Monitoring the lithiasic phenotype by X-ray, urine amino acid content analysis and protein expression studies have shown that double heterozygous mice (Slc7a9+/-Slc3a1+/-) present lower expression of system b0,+ and higher hyperexcretion of cystine than single heterozygotes (Slc7a9+/-Slc3a1+/+ and Slc7a9+/+Slc3a1+/-) and give rise to lithiasis in 4% of the mice, demonstrating that cystinuria has a digenic inheritance in this mouse model. Moreover in this study it has been demonstrated a genotype/phenotype correlation in type AB cystinuria mouse model providing new insights for further molecular and genetic studies of cystinuria patients. |
| publishDate |
2015 |
| dc.date.none.fl_str_mv |
2015 |
| 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/2445/99860 |
| url |
https://hdl.handle.net/2445/99860 |
| dc.language.none.fl_str_mv |
Inglés |
| language_invalid_str_mv |
Inglés |
| dc.relation.none.fl_str_mv |
Reproducció del document publicat a: http://dx.doi.org/10.1371/journal.pone.0137277 PLoS One, 2015, vol. 10, num. 9, p. e0137277 http://dx.doi.org/10.1371/journal.pone.0137277 |
| dc.rights.none.fl_str_mv |
cc-by (c) Espino, Meritxell et al., 2015 http://creativecommons.org/licenses/by/3.0/es info:eu-repo/semantics/openAccess |
| rights_invalid_str_mv |
cc-by (c) Espino, Meritxell et al., 2015 http://creativecommons.org/licenses/by/3.0/es |
| eu_rights_str_mv |
openAccess |
| dc.format.none.fl_str_mv |
application/pdf |
| dc.publisher.none.fl_str_mv |
Public Library of Science (PLoS) |
| publisher.none.fl_str_mv |
Public Library of Science (PLoS) |
| dc.source.none.fl_str_mv |
Articles publicats en revistes (Ciències Fisiològiques) reponame:Dipòsit Digital de la UB instname:Universidad de Barcelona |
| instname_str |
Universidad de Barcelona |
| reponame_str |
Dipòsit Digital de la UB |
| collection |
Dipòsit Digital de la UB |
| repository.name.fl_str_mv |
|
| repository.mail.fl_str_mv |
|
| _version_ |
1869417471016960000 |
| score |
15,301603 |