The kd/kd mouse is a model of collapsing Glomerulopathy

Collapsing glomerulopathy (CG) is associated with disorders that markedly perturb the phenotype of podocytes. The kd/kd mouse has been studied for immune and genetic causes of microcystic tubulointerstitial nephritis with little attention to its glomerular lesion. Because histologic examination revealed classic morphologic features of CG, the question arises whether podocytes in kd/kd mice exhibit additional phenotypic criteria for CG. Utilizing Tg26 mice as a positive control, immunohistochemical profiling of the podocyte phenotype was conducted simultaneously on both models. Similar to Tg26 kidneys, podocytes in kd/kd kidneys showed de novo cyclin D1, Ki-67, and desmin expression with loss of synaptopodin and WT-1 expression. Electron micrographs showed collapsed capillaries, extensive foot process effacement, and dysmorphic mitochondria in podocytes. These results indicate that the kd/kd mouse is a model of CG and raise the possibility that human equivalents of the kd susceptibility gene may exist in patients with CG.