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Adenine phosphoribosyltransferase-deficient mice develop 2,8-dihydroxyadenine nephrolithiasis
S J Engle1, M G Stockelman, J Chen
1Department of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, 46202-5251, USA.
Summary
Adenine phosphoribosyltransferase (APRT) deficiency causes kidney stones due to adenine and 2,8-dihydroxyadenine (DHA) excretion. APRT-deficient mice mimic this human disease, offering a valuable model for hereditary nephrolithiasis research.
Area of Science:
- Biochemistry
- Genetics
- Nephrology
Background:
- Adenine phosphoribosyltransferase (APRT) deficiency is an inherited disorder.
- It leads to kidney stones and renal failure due to 2,8-dihydroxyadenine (DHA) accumulation.
- A suitable animal model is needed to study this condition.
Purpose of the Study:
- To create and characterize a mouse model of APRT deficiency.
- To investigate the biochemical and histological manifestations of the disease in mice.
Main Methods:
- Targeted homologous recombination in embryonic stem cells was used to generate APRT-deficient mice.
- Urine and kidney tissues were analyzed for adenine, DHA, and histopathological changes.
Main Results:
- APRT-deficient mice excreted adenine and DHA crystals in urine.
- Renal histopathology revealed tubular dilation, inflammation, necrosis, and fibrosis.
- These changes varied in severity depending on the mouse genetic background.
Conclusions:
- APRT-deficient mice accurately replicate the biochemical and pathological features of human APRT deficiency.
- This mouse model serves as a valuable tool for studying hereditary nephrolithiasis and developing therapeutic strategies.