Kidney failure in mice lacking the tetraspanin CD151.
The tetraspanin CD151 is a cell-surface molecule known for its strong lateral interaction with the laminin-binding integrin alpha3beta1. Patients with a nonsense mutation in CD151 display end-stage kidney failure associated with regional skin blistering and sensorineural deafness, and mice lacking the integrin alpha3 subunit die neonatally because of severe abnormalities in the lung and kidney epithelia. We report the generation of Cd151-null mice that recapitulate the renal pathology of human patients, i.e., with age they develop massive proteinuria caused by focal glomerulosclerosis, disorganization of the glomerular basement membrane, and tubular cystic dilation. However, neither skin integrity nor hearing ability are impaired in the Cd151-null mice. Furthermore, we generated podocyte-specific conditional knockout mice for the integrin alpha3 subunit that show renal defects similar to those in the Cd151 knockout mice. Our results support the hypothesis that CD151 plays a key role in strengthening alpha3beta1-mediated adhesion in podocytes.
Sachs
Norman
N
Division of Cell Biology, The Netherlands Cancer Institute, 1066 CX Amsterdam, Netherlands.
Kreft
Maaike
M
van den Bergh Weerman
Marius A
MA
Beynon
Andy J
AJ
Peters
Theo A
TA
Weening
Jan J
JJ
Sonnenberg
Arnoud
A
D000818:Animals; D015703:Antigens, CD / Q000235:genetics*; D002448:Cell Adhesion; D005838:Genotype; D050533:Glomerular Basement Membrane / Q000473:pathology; D039422:Integrin alpha3 / Q000235:genetics; D039201:Integrin alpha3beta1 / Q000502:physiology; D007684:Kidney Tubules / Q000473:pathology; D051379:Mice; D009154:Mutation; D050199:Podocytes / Q000166:cytology; D051437:Renal Insufficiency / Q000235:genetics*; D060185:Tetraspanin 24
D015703:Antigens, CD; C554715:CD151 protein, human; C554716:Cd151 protein, mouse; D039422:Integrin alpha3; D039201:Integrin alpha3beta1; D060185:Tetraspanin 24