Please use this identifier to cite or link to this item: http://hdl.handle.net/2445/99860
Title: Digenic inheritance in cystinuria mouse model
Author: Espino, Meritxell
Font i Llitjós, Mariona
Vilches, Clara
Salido, Eduardo
Prat, Esther
López de Heredia, Miguel
Palacín Prieto, Manuel
Nunes Martínez, Virginia
Keywords: 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
Issue Date: 11-Sep-2015
Publisher: Public Library of Science (PLoS)
Abstract: 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.
Note: Reproducció del document publicat a: http://dx.doi.org/10.1371/journal.pone.0137277
It is part of: PLoS One, 2015, vol. 10, num. 9, p. e0137277
Related resource: http://dx.doi.org/10.1371/journal.pone.0137277
URI: http://hdl.handle.net/2445/99860
ISSN: 1932-6203
Appears in Collections:Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL))
Articles publicats en revistes (Ciències Fisiològiques)
Articles publicats en revistes (Bioquímica i Biomedicina Molecular)
Articles publicats en revistes (Institut de Recerca Biomèdica (IRB Barcelona))

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