title: Kidney failure in mice lacking the tetraspanin CD151.
abstract: 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.
authors.affiliation: Division of Cell Biology, The Netherlands Cancer Institute, 1066 CX Amsterdam, Netherlands.
authors.forename: Norman
authors.initials: N
authors.lastname: Sachs
authors.forename: Maaike
authors.initials: M
authors.lastname: Kreft
authors.forename: Marius A
authors.initials: MA
authors.lastname: van den Bergh Weerman
authors.forename: Andy J
authors.initials: AJ
authors.lastname: Beynon
authors.forename: Theo A
authors.initials: TA
authors.lastname: Peters
authors.forename: Jan J
authors.initials: JJ
authors.lastname: Weening
authors.forename: Arnoud
authors.initials: A
authors.lastname: Sonnenberg
mesh_terms: 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
chemical_list: D015703:Antigens, CD; C554715:CD151 protein, human; C554716:Cd151 protein, mouse; D039422:Integrin alpha3; D039201:Integrin alpha3beta1; D060185:Tetraspanin 24