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...

ver descrição completa

Detalhes bibliográficos
Autores: Espino Gaurch, Meritxell, Font i Llitjós, Mariona, Vilches, Clara, Salido, Eduardo, Prat, Esther, López de Heredia, Miguel, Palacín Prieto, Manuel, Nunes Martínez, Virginia
Formato: artículo
Estado:Versión publicada
Fecha de publicación:2015
País:España
Recursos: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:2445/99860
Acesso em linha:https://hdl.handle.net/2445/99860
Access Level:acceso abierto
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_e1d2551822e06d1bd5445257fdcd2ebf
oai_identifier_str oai:recercat.cat: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)2016201620152016info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersion12 p.application/pdfhttps://hdl.handle.net/2445/99860Articles 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: 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:recercat.cat:2445/998602026-05-29T05:05:01Z
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
2016
2016
2016
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 12 p.
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: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
_version_ 1869422328585125888
score 15,811543