CD2-associated protein (CD2AP) expression in podocytes rescues lethality of CD2AP deficiency.
Mice born without CD2-associated protein (CD2AP) develop renal failure and nephrotic syndrome about 4 weeks after birth and die around 6 weeks of age. Although CD2AP is widely expressed, the severity of the renal failure precludes a clear determination of the role of CD2AP in other tissues. Here we generated transgenic mice expressing CD2AP using a podocyte-specific promoter. Podocyte-specific expression of CD2AP prevented the development of proteinuria, demonstrating that the renal failure is solely due to loss of CD2AP in podocytes and not in other renal or in immune cells. CD2AP-deficient mice are long-lived and appear phenotypically normal. Histological analysis demonstrated testicular abnormalities that were age-related. CIN85, a paralog of CD2AP, is poorly expressed in both the podocyte and the basal seminiferous tubule, suggesting that the loss of CD2AP in specific tissues may be compensated for by CIN85.
Grunkemeyer
James A
JA
Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, Missouri 63110, USA.
Kwoh
Christopher
C
Huber
Tobias B
TB
Shaw
Andrey S
AS
D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D003598:Cytoskeletal Proteins; D004847:Epithelial Cells / Q000378:metabolism*; D007248:Infertility, Male / Q000209:etiology; D007678:Kidney Glomerulus / Q000166:cytology*; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D010641:Phenotype; D011506:Proteins / Q000502:physiology*; D051437:Renal Insufficiency / Q000209:etiology / Q000517:prevention & control; D013737:Testis / Q000473:pathology
D048868:Adaptor Proteins, Signal Transducing; C114545:CD2-associated protein; D003598:Cytoskeletal Proteins; D011506:Proteins