An animal model of type A cystinuria due to spontaneous mutation in 129S2/SvPasCrl mice.

Abstract

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.

• Authors: Marine Livrozet, Sophie Vandermeersch, Laurent Mesnard, Elizabeth Thioulouse, Jean Jaubert, Jean-Jacques Boffa, Jean-Philippe Haymann, Laurent Baud, Dominique Bazin, Michel Daudon, Emmanuel Letavernier
• Journal: PloS one (PLoS One) Vol. 9 Issue 7 Pg. e102700 ( 2014) ISSN: 1932-6203 [Electronic] United States
• PMID: 25048459 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Amino Acid Transport Systems, Basic
• Amino Acid Transport Systems, Neutral
• Slc3a1 protein, mouse

Topics

• Amino Acid Sequence
• Amino Acid Transport Systems, Basic (chemistry, genetics)
• Amino Acid Transport Systems, Neutral (chemistry, genetics)
• Animals
• Cystinuria (complications, genetics, physiopathology)
• Disease Models, Animal
• Kidney (metabolism, physiopathology)
• Kidney Calculi (etiology, genetics, physiopathology)
• Male
• Mice
• Mice, Inbred C57BL
• Molecular Sequence Data
• Mutation, Missense
• Phenotype