Characterization of novel kidney specific manganese superoxide dismutase knockout mice

Inactivation of manganese superoxide dismutase (MnSOD), the major mitochondrial antioxidant, is a key issue in renal failure following transplantation or ischemia/reperfusion (IR) injury. Homozygous MnSOD knock out (KO) mice die shortly after birth, and heterozygous MnSOD KO mice have decreased MnSOD activity in all tissues/organs. To address the role MnSOD inactivation has on renal injury, we generated bi‐transgenic kidney specific MnSOD KO (50% and 100%) mice by breeding KidneyCre mice 1 and floxed MnSOD mice 2 . Characterization of these KOs revealed that phenotypically the mice are smaller in size compared to littermate controls, but show no survival differences. Immunohistochemistry data showed that the Cre‐recombinase mediated MnSOD deletion occurred specifically in the kidney and was located predominantly in the medullary region. The kidney specific KOs exhibited histologic evidence of mild renal damage, increased tyrosine nitration, and renal cell death. KO mice renal function was not altered; however, more renal damage was observed following IR injury compared to littermate controls. In summary, we have developed a novel kidney specific MnSOD KO mouse model that will help define the molecular pathways that occur downstream of MnSOD inactivation during renal injury. Supported by NIH grant 1RO1DK0789361.