The glomerulosclerosis gene Mpv17 encodes a peroxisomal protein producing reactive oxygen species.
The mutant mouse strain Mpv17 carries a retroviral insert in its genome which inactivates the Mpv17 gene. At a young age these mice develop glomerulosclerosis and nephrotic syndrome which resembles human disease. We show here that the Mpv17 gene product is highly conserved and encodes a peroxisomal protein. Loss of the Mpv17 protein does not impair peroxisome biogenesis but instead leads to a reduced ability to produce reactive oxygen species (ROS). In turn, overproduction of the Mpv17 gene in transfected cells results in dramatically enhanced levels of intracellular ROS indicating a direct involvement of Mpv17 in ROS production. These data reveal a role for the Mpv17 protein in peroxisomal reactive oxygen metabolism and establish a novel link between peroxisomal ROS production and glomerulosclerosis.
Zwacka
R M
RM
Kernforschungszentrum Karlsruhe, Institut für Genetik, Karlsruhe, Germany.
Reuter
A
A
Pfaff
E
E
Moll
J
J
Gorgas
K
K
Karasawa
M
M
Weiher
H
H
D000595:Amino Acid Sequence; D000818:Animals; D002374:Catalase / Q000302:isolation & purification; D002451:Cell Compartmentation; D004195:Disease Models, Animal; D005347:Fibroblasts / Q000648:ultrastructure; D005455:Fluorescent Antibody Technique; D005921:Glomerulonephritis / Q000235:genetics*; D008099:Liver / Q000648:ultrastructure; D008565:Membrane Proteins; D051379:Mice; D008817:Mice, Mutant Strains; D008830:Microbodies / Q000378:metabolism*; D008969:Molecular Sequence Data; D009404:Nephrotic Syndrome / Q000235:genetics*; D011506:Proteins / Q000235:genetics* / Q000302:isolation & purification / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism*; D017386:Sequence Homology, Amino Acid
D008565:Membrane Proteins; C065292:Mpv17 protein, mouse; D011506:Proteins; D017382:Reactive Oxygen Species; D002374:Catalase