An animal model of type A cystinuria due to spontaneous mutation in 129S2/SvPasCrl mice.
2014
Cystinuriais 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
cystinecrystals in urine and an
aminoaciduriaprofile similar to that of patients with
cystinuria. In addition, we observed a heterogeneous inflammatory infiltrate and
cystinetubular 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 tubulesand 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.
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