CD2-associated protein haploinsufficiency is linked to glomerular disease susceptibility.

Loss of CD2-associated protein (CD2AP), a component of the filtration complex in the kidney, causes death in mice at 6 weeks of age. Mice with CD2AP haploinsufficiency developed glomerular changes at 9 months of age and had increased susceptibility to glomerular injury by nephrotoxic antibodies or immune complexes. Electron microscopic analysis of podocytes revealed defects in the formation of multivesicular bodies, suggesting an impairment of the intracellular degradation pathway. Two human patients with focal segmental glomerulosclerosis had a mutation predicted to ablate expression of one CD2AP allele, implicating CD2AP as a determinant of human susceptibility to glomerular disease.