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

[cystinuria]

Cystinuria is an autosomal recessive disease caused by the mutation of either SLC 3 A 1 gene encoding for rBAT (type A cystinuria ) or SLC 7 A 9 gene encoding for b 0 ,+AT (type B cystinuria ). Here , we evidenced in a commonly used congenic 129 S 2 /SvPasCrl mouse substrain a dramatically high frequency of kidney stones that were similar to those of patients with cystinuria . Most of 129 S 2 /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 , C 5 7 BL /6 J mice , 129 S 2 /SvPasCrl mice had an increased mortality associated with bilateral obstructive hydronephrosis . In 129 S 2 /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 Slc 3 a 1 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 .