BACKGROUND: Cystinosis is caused by mutations in CTNS that encodes cystinosin, the lysosomal cystine transporter. The most severe and frequent form is characterized by a proximal tubulopathy that appears around 6 to 12 months of age. In the absence of treatment, end-stage renal disease is reached by 10 years. Ctns(-/-) mice of a mixed 129Sv x C57BL/6 genetic background show elevated renal cystine levels; however, proximal tubulopathy or end-stage renal disease is not observed. METHODS: As renal phenotype can be influenced by genetic background, we generated congenic C57BL/6 and FVB/N Ctns(-/-) mice and assayed renal lesions and function by histological and biochemical studies. RESULTS: C57BL/6 Ctns(-/-) mice showed significantly higher renal cystine levels than the FVB/N strain. Moreover, C57BL/6 mice presented with pronounced histological lesions of the proximal tubules as well as a tubulopathy and progressively developed chronic renal failure. In contrast, renal dysfunction was not observed in the FVB/N strain. CONCLUSIONS: Thus, the C57BL/6 strain represents the first Ctns(-/-) mouse model to show clear renal defects. In addition to highlighting the influence of genetic background on phenotype, the C57BL/6 Ctns(-/-) mice represent a useful model for further understanding cystinosin function in the kidney and, specifically, in the proximal tubules.
Renal phenotype of the cystinosis mouse model is dependent upon genetic background
Nevo, N.; Chol, M.; Bailleux, A.; Kalatzis, V.; Morisset, L.; Devuyst, O.; Gubler, M. C.; Antignac, C.
Nephrol Dial Transplant
2010-04 / vol 25 / pages 1059-66
10.1093/ndt/gfp553 gfp553 [pii]
1460-2385 (Electronic) 0931-0509 (Linking)
Female; Animals; Mice; Mice, Knockout; Male; Phenotype; Mice, Inbred C57BL; Mutation/genetics; *Disease Models, Animal; Amino Acid Transport Systems, Neutral/*physiology; Cystine/*metabolism; Cystinosis/*etiology/pathology; Kidney Failure, Chronic/*etiology/pathology; Species Specificity