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Sequential analysis of kidney stone formation in the Aprt knockout mouse
A P Evan1, S B Bledsoe, B A Connors
1Department of Anatomy and Cell Biology, Indiana University School of Medicine, Indianapolis, Indiana 46202-5120, USA. evan@anatomy.iupui.edu
Kidney International
|September 5, 2001
Summary
Male Aprt knockout mice develop more severe 2,8-dihydroxyadenine (DHA) kidney stones and renal pathology than females. This study quantifies DHA crystal accumulation and correlates it with histopathology in male and female mice.
Area of Science:
- Nephrology
- Genetics
- Biochemistry
Background:
- Adenine phosphoribosyltransferase (APRT) deficiency causes 2,8-dihydroxyadenine (DHA) renal stones in humans.
- Aprt knockout mice models exhibit similar DHA stone formation, with earlier and more severe disease in males.
- Investigating sex-based differences in DHA stone formation and renal pathology is crucial.
Purpose of the Study:
- To quantify DHA crystal accumulation in the kidneys of male and female Aprt knockout mice.
- To correlate DHA crystal burden with renal histopathology.
- To elucidate the biological basis for sex-based differences in Aprt deficiency disease severity.
Main Methods:
- Kidney cryosections from Aprt knockout mice (aged one day to eight months) were analyzed for birefringent DHA crystals using polarized light microscopy.
- Renal histopathology was assessed in plastic-embedded, stained sections, and a pathological score was assigned.
- Two-way ANOVA was used to analyze crystal area and pathology scores; X-ray diffraction and SEM identified crystal composition and morphology.
Main Results:
- DHA crystals were detected in Aprt knockout mice from one to two days old.
- Males showed a significantly higher crystal burden and renal pathology (interstitial fibrosis) between 120 and 240 days old compared to females.
- Aprt heterozygotes and wild-type mice showed minimal to no crystalline material or pathology.
Conclusions:
- Both male and female Aprt knockout mice accumulate DHA, but males exhibit significantly greater crystal burden and renal pathology at specific ages.
- The study highlights a sex-based disparity in the severity of DHA nephropathy in the Aprt knockout mouse model.
- These findings provide insights into the biological mechanisms underlying sex differences in kidney stone disease.
