Adenine phosphoribosyltransferase-deficient mice develop 2,8-dihydroxyadenine nephrolithiasis.
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.
Engle
S J
SJ
Department of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, 46202-5251, USA.
Stockelman
M G
MG
Chen
J
J
Boivin
G
G
Yum
M N
MN
Davies
P M
PM
Ying
M Y
MY
Sahota
A
A
Simmonds
H A
HA
Stambrook
P J
PJ
Tischfield
J A
JA
D000225:Adenine / Q000031:analogs & derivatives / Q000652:urine; D000228:Adenine Phosphoribosyltransferase / Q000097:blood / Q000172:deficiency* / Q000235:genetics*; D000483:Alleles; D000818:Animals; D004912:Erythrocytes / Q000201:enzymology; D005355:Fibrosis; D006720:Homozygote; D006801:Humans; D007249:Inflammation; D007668:Kidney / Q000473:pathology; D007669:Kidney Calculi / Q000235:genetics* / Q000473:pathology / Q000652:urine; D051379:Mice; D018345:Mice, Knockout; D009336:Necrosis; D011995:Recombination, Genetic; D015183:Restriction Mapping; D013234:Stem Cells
C002993:2,8-dihydroxyadenine; D000228:Adenine Phosphoribosyltransferase; D000225:Adenine