Adenine Phosphoribosyltransferase-deficient Mice Develop 2,8-dihydroxyadenine Nephrolithiasis

Overview

Journal Proc Natl Acad Sci U S A

Specialty Science

Date 1996 May 28

PMID 8643571

Citations 32

Authors

S J Engle

M G Stockelman

J Chen

G Boivin

M N Yum

P M Davies

M Y Ying

A Sahota

H A Simmonds

P J Stambrook

J A Tischfield

Affiliations

Soon will be listed here.

Abstract

Adenine phosphoribosyltransferase (APRT) deficiency in humans is an autosomal recessive syndrome characterized by the urinary excretion of adenine and the highly insoluble compound 2,8-dihydroxyadenine (DHA) that can produce kidney stones or renal failure. Targeted homologous recombination in embryonic stem cells was used to produce mice that lack APRT. Mice homozygous for a null Aprt allele excrete adenine and DHA crystals in the urine. Renal histopathology showed extensive tubular dilation, inflammation, necrosis, and fibrosis that varied in severity between different mouse backgrounds. Thus, biochemical and histological changes in these mice mimic the human disease and provide a suitable model of human hereditary nephrolithiasis.

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