An Animal Model of Type A Cystinuria Due to Spontaneous Mutation in 129S2/SvPasCrl Mice

Cystinuria is an autosomal recessive disease caused by the mutation of either SLC3A1 gene encoding for rBAT (type A cystinuria) or SLC7A9 gene encoding for b0,+AT (type B cystinuria). Here, we evidenced in a commonly used congenic 129S2/SvPasCrl mouse substrain a dramatically high frequency of kidne...

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Published in	PloS one Vol. 9; no. 7; p. e102700
Main Authors	Livrozet, Marine, Vandermeersch, Sophie, Mesnard, Laurent, Thioulouse, Elizabeth, Jaubert, Jean, Boffa, Jean-Jacques, Haymann, Jean-Philippe, Baud, Laurent, Bazin, Dominique, Daudon, Michel, Letavernier, Emmanuel
Format	Journal Article
Language	English
Published	United States Public Library of Science 21.07.2014 Public Library of Science (PLoS)
Subjects	Amino Acid Sequence Amino Acid Transport Systems, Basic - chemistry Amino Acid Transport Systems, Basic - genetics Amino Acid Transport Systems, Neutral - chemistry Amino Acid Transport Systems, Neutral - genetics Amino acids Analysis Animal models Animals Biology and Life Sciences Casts Crystals Cysteine Cystine Cystinuria Cystinuria - complications Cystinuria - genetics Cystinuria - physiopathology Disease Models, Animal Genetic aspects House mouse Human health and pathology Inflammation Kidney - metabolism Kidney - physiopathology Kidney Calculi - etiology Kidney Calculi - genetics Kidney Calculi - physiopathology Kidney diseases Kidney stones Kidneys Laboratory animals Life Sciences Lithiasis Male Medicine and Health Sciences Mice Mice, Inbred C57BL Mimicry Molecular Sequence Data Mutation Mutation, Missense Nephrolithiasis Patients Phenotype Proximal tubules Renal aminoaciduria Scanning electron microscopy Transporter Tubules Urine France United States > US
Online Access	Get full text
ISSN	1932-6203 1932-6203
DOI	10.1371/journal.pone.0102700

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Summary:	Cystinuria is an autosomal recessive disease caused by the mutation of either SLC3A1 gene encoding for rBAT (type A cystinuria) or SLC7A9 gene encoding for b0,+AT (type B cystinuria). Here, we evidenced in a commonly used congenic 129S2/SvPasCrl mouse substrain a dramatically high frequency of kidney stones that were similar to those of patients with cystinuria. Most of 129S2/SvPasCrl exhibited pathognomonic cystine crystals in urine and an aminoaciduria profile similar to that of patients with cystinuria. In addition, we observed a heterogeneous inflammatory infiltrate and cystine tubular casts in the kidney of cystinuric mice. As compared to another classical mouse strain, C57BL/6J mice, 129S2/SvPasCrl mice had an increased mortality associated with bilateral obstructive hydronephrosis. In 129S2/SvPasCrl mice, the heavy subunit rBAT of the tetrameric transporter of dibasic amino acids was absent in proximal tubules and we identified a single pathogenic mutation in a highly conserved region of the Slc3a1 gene. This novel mouse model mimicking human disease would allow us further pathophysiological studies and may be useful to analyse the crystal/tissue interactions in cystinuria.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 14 content type line 23 Competing Interests: The authors have declared that no competing interests exist. Conceived and designed the experiments: ML SV LM ET MD EL. Performed the experiments: ML SV LM ET MD DB JJ EL. Analyzed the data: ML SV LM ET JJB JPH LB MD DB EL. Contributed reagents/materials/analysis tools: ML SV LM ET JJB JPH LB MD DB JJ EL. Wrote the paper: ML LB JJ EL.
ISSN:	1932-6203 1932-6203
DOI:	10.1371/journal.pone.0102700