Proteinuria in AMPD2-deficient mice.
The AMPD2 gene, a member of the AMPD gene family encoding AMP deaminase, is widely expressed in nonmuscle tissues including kidney, although its functions have not been fully elucidated. In this study, we studied the function of the AMPD2 gene by establishing AMPD2-deficient model animal. We established AMPD2 knockout mice by using gene transfer and homologous recombination in murine ES cells and studied phenotypes and functions in the kidneys of these animals. AMPD activity was decreased from 22.9 mIU/mg protein to 2.5 mIU/mg protein in the kidneys of AMPD knockout mice. In addition to changes in nucleotide metabolism in the kidneys, proteinuria was found in 3-week-old AMPD2 knockout mice, followed by a further increment up to a peak level at 6 weeks old (up to 0.6 g/dL). The major protein component in the urine of AMPD2 knockout mice was found to be albumin, indicating that AMPD2 may have a key role in glomerular filtration. Indeed, an ultrastructure study of glomerulus specimens from these mice showed effacement of the podocyte foot processes, resembling minimal-change nephropathy in humans. Based on our results, we concluded that AMPD2 deficiency induces imbalanced nucleotide metabolism and proteinuria, probably due to podocyte dysfunction.
Department of Bioscience and Genetics, National Cerebral and Cardiovascular Center Research Institute, 5-7-1 Fujishirodai, Suita, Osaka 565-8565, Japan.
Keiko
K
Toyama
Hiroko
H
Morisaki
Jidong
J
Cheng
Hiroshi
H
Kawachi
Fujio
F
Shimizu
Masahito
M
Ikawa
Masaru
M
Okabe
Takayuki
T
Morisaki
D000659:AMP Deaminase / Q000172:deficiency / Q000235:genetics; D000818:Animals; D007668:Kidney / Q000378:metabolism*; D007678:Kidney Glomerulus / Q000378:metabolism / Q000473:pathology*; D051379:Mice; D018345:Mice, Knockout; D009709:Nucleotide Deaminases / Q000378:metabolism*; D009711:Nucleotides / Q000378:metabolism*; D011507:Proteinuria / Q000235:genetics* / Q000378:metabolism; D011686:Purine-Pyrimidine Metabolism, Inborn Errors / Q000235:genetics / Q000473:pathology / Q000503:physiopathology*
D009711:Nucleotides; D009709:Nucleotide Deaminases; D000659:AMP Deaminase; C000592119:AMPD2 protein, mouse