Digenic inheritance in cystinuria mouse model

Meritxell Espino Guarch, Mariona Font-Llitjós, Clara Vilches, Eduardo Salido, Esther Prat, Miguel López De Heredia, Manuel Palacín, Virginia Nunes, Yann Herault

Research output: Contribution to journalArticle

3 Citations (Scopus)

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.

Original languageEnglish
Article numbere0137277
JournalPLoS One
Volume10
Issue number9
DOIs
Publication statusPublished - 11 Sep 2015
Externally publishedYes

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Cystinuria
Cystine
cystine
inheritance (genetics)
animal models
mutation
amino acids
mice
Diamino Amino Acids
urine
renal calculi
Amino Acid Transport Systems
signs and symptoms (animals and humans)
heterozygosity
X-radiation
Mutation
protein synthesis
Genes
kidneys
phenotype

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Espino Guarch, M., Font-Llitjós, M., Vilches, C., Salido, E., Prat, E., De Heredia, M. L., ... Herault, Y. (2015). Digenic inheritance in cystinuria mouse model. PLoS One, 10(9), [e0137277]. https://doi.org/10.1371/journal.pone.0137277

Digenic inheritance in cystinuria mouse model. / Espino Guarch, Meritxell; Font-Llitjós, Mariona; Vilches, Clara; Salido, Eduardo; Prat, Esther; De Heredia, Miguel López; Palacín, Manuel; Nunes, Virginia; Herault, Yann.

In: PLoS One, Vol. 10, No. 9, e0137277, 11.09.2015.

Research output: Contribution to journalArticle

Espino Guarch, M, Font-Llitjós, M, Vilches, C, Salido, E, Prat, E, De Heredia, ML, Palacín, M, Nunes, V & Herault, Y 2015, 'Digenic inheritance in cystinuria mouse model', PLoS One, vol. 10, no. 9, e0137277. https://doi.org/10.1371/journal.pone.0137277
Espino Guarch M, Font-Llitjós M, Vilches C, Salido E, Prat E, De Heredia ML et al. Digenic inheritance in cystinuria mouse model. PLoS One. 2015 Sep 11;10(9). e0137277. https://doi.org/10.1371/journal.pone.0137277
Espino Guarch, Meritxell ; Font-Llitjós, Mariona ; Vilches, Clara ; Salido, Eduardo ; Prat, Esther ; De Heredia, Miguel López ; Palacín, Manuel ; Nunes, Virginia ; Herault, Yann. / Digenic inheritance in cystinuria mouse model. In: PLoS One. 2015 ; Vol. 10, No. 9.
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