Insulin receptor- related receptor (IRR) is a novel receptor tyrosine kinase in the insulin receptor family. Unlike its fellow family members insulin receptor and insulin- like growth factor type 1 receptor, the ligand for IRR is unknown. In addition, IRR mRNA has a very limited tissue distribution in comparison with insulin receptor and insulin- like growth factor type 1 receptor. Previous studies have demonstrated that the mammalian organ with the highest level of IRR transcript is the kidney. By in situ hybridization, kidney expression of IRR mRNA is only in the distal nephron; however, the specific cellular distribution of IRR is unknown. The purpose of this study was to examine IRR protein expression in the mouse kidney using immunohistochemical techniques.

Consistent with the in situ hybridization studies, IRR protein was not present in the glomeruli, the proximal tubules, or the loops of Henle. IRR was specifically present in a subset of cells in the connecting tubule, the initial collecting tubule, and the cortical collecting duct. IRR protein was detected in cells which express vacuolar H+ATPase and carbonic anhydrase II, but not in cells which express band 3 (AE1). In the cortical collecting duct, the IRR positive cells are likely B intercalated cells. In the connecting tubule and the initial collecting tubule, the cells are B cells and/ or Non-A Non-B cells. Thus IRR is a specific marker for Non-A intercalated cells. IRR may be used as an immunohistochemical label for the developmental tracking of B cells and possibly Non-A Non- B cells to the distal nephron during nephrogenesis. In addition, the IRR receptor tyrosine kinase may participate in the functional specialization of B intercalated cells or Non-A Non-B cells, including mediating phenotypic changes which occur in response to disturbances in systemic acid- base balance.