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Nephrol Dial Transplant. 2010 Apr;25(4):1059-66. doi: 10.1093/ndt/gfp553. Epub 2009 Oct 21.

Renal phenotype of the cystinosis mouse model is dependent upon genetic background.

Author information

1
Inserm, U574, Hôpital Necker-Enfants Malades, Paris, France.

Abstract

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.

PMID:
19846395
DOI:
10.1093/ndt/gfp553
[Indexed for MEDLINE]

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