Our inventors have discovered a novel mechanism of hyperglycemia-induced hyperfiltration via the NOS1 and NKCC2 proteins within the body. By increasing the level of luminal glucose at the macula densa, neuronal NOS1 (Nitric Oxide Synthase 1) becomes active, which halts the TGF response. Three different mouse model lineages were created to analyze the distinct properties of the NKCC2 and NOS1 involvement during an acute hyperglycemic state. The NKCC2flox mouse model displays a deleted NKCC2 gene, which disrupts the communication between NOS1 and the TGF response. The NOS1Cre mouse model upholds full functionality of the NOS1 gene, and targets all splice variants of NOS1. The NOS1Cre-NKCC2flox mouse model exemplifies a deleted NKCC2 gene in the macula densa cells and the TGF response is lost. The mouse models produced from this technology will allow for further research of the glomerular hyperfiltration mechanism, diabetic nephropathy, and associated diseases.