1. Renal phenotype of the cystinosis mouse model is dependent upon genetic background
- Author
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Ludivine Morisset, Marie-Claire Gubler, Nathalie Nevo, Marie Chol, Corinne Antignac, Olivier Devuyst, Anne Bailleux, Vasiliki Kalatzis, Institut de Génétique Moléculaire de Montpellier (IGMM), Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM), UCL - SSS/IREC/NEFR - Pôle de Néphrologie, and UCL - (SLuc) Service de néphrologie
- Subjects
Male ,Pathology ,Amino Acid Transport Systems ,medicine.medical_treatment ,Cystinosis ,030232 urology & nephrology ,Neutral/*physiology Animals Cystine/*metabolism Cystinosis/*etiology/pathology *Disease Models ,Mice ,0302 clinical medicine ,cystinosis genetic background ,Knockout Mutation/genetics Phenotype Species Specificity ,Mice, Knockout ,0303 health sciences ,Kidney ,medicine.anatomical_structure ,Phenotype ,Cystinosin ,Nephrology ,Cystine ,Female ,Hemodialysis ,medicine.medical_specialty ,Inbred C57BL Mice ,mouse model ,Congenic ,proximal tubule dysfunction ,Animal Female Kidney Failure ,03 medical and health sciences ,Tubulopathy ,Species Specificity ,chronic renal failure ,Internal medicine ,medicine ,Animals ,[SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology ,030304 developmental biology ,Transplantation ,business.industry ,Fanconi syndrome ,medicine.disease ,Mice, Inbred C57BL ,Disease Models, Animal ,Endocrinology ,Amino Acid Transport Systems, Neutral ,Chronic/*etiology/pathology Male Mice Mice ,Mutation ,Kidney Failure, Chronic ,business ,Kidney disease - 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.
- Published
- 2010