Proteomic analysis of a model of nephronophthisis type 2

INVS gene mutations cause cystic kidney disease in children with infantile nephronophthisis (NPH 2), but protein alterations at the cellular level are not precisely defined in affected kidneys. The purpose of our study was to identify differentially expressed proteins in kidneys of inv/inv mice, a model of NPH2. We used a proteomic approach to target in vivo proteins that are misexpressed in the absence of inversin. We hypothesize that loss of inversin alters expression of proteins that participate in subcellular multi‐protein pathways involved in gene transcription and maintenance of renal epithelial cell polarity, extracellular matrix or cilium‐mediated calcium signaling. We performed proteomic analysis of kidney tissue lysates from newborn inv/inv mice (n = 22 kidneys divided into two groups) and +/+ control mice (n = 42 kidneys divided into two groups). Two‐dimensional polyacrylamide gel electrophoresis of lysates was performed in quadruplicate using a pH range of 3–10 and 10–18% linear gradient SDS‐PAGE gel. Coomassie stained gels contained ~1000 detectable protein spots in inv / inv and +/+ kidneys. We selected 101 of the most differentially expressed proteins for protein identification. The majority of protein identifications fit within two classifications, transcription and signal transduction/cell communication. Proteomic analysis of inv/inv mouse kidney provides new information about protein expression and regulation in a mouse model that mimics NPH2. Identification of these proteins will contribute to our understanding of intracellular protein networks involving inversin and lead to novel insights regarding the pathogenesis of renal cysts.