Ablation of Hoxb3os in mouse polycystic kidney disease exacerbates cystogenesis

Autosomal dominant polycystic kidney disease (ADPKD) is a monogenic disorder characterized by the formation of cysts in the kidney and is primarily caused by mutations in two genes, PKD1 and PKD2. In this study, we investigated the role of the long noncoding RNA (lncRNA) Hoxb3os in ADPKD by ablating its expression in the mouse. Hoxb3os-null mice were viable and had grossly normal kidney morphology but displayed activation of mTOR/Akt signaling and subsequent increase in kidney cell proliferation. To determine the role of Hoxb3os in cystogenesis, we crossed the Hoxb3os-null mouse to two orthologous Pkd1 mouse models: Pkhd1/Cre;Pkd1F/F (rapid cyst progression) and Pkd1RC/RC (slow cyst progression). Ablation of Hoxb3os exacerbated cyst growth in both models. To gain insight into the mechanism whereby Hoxb3os inhibition promotes cystogenesis, we performed proteomic analysis of mTOR/Akt pathway between Pkd1 single-knockout (SKO) and Pkd1-Hoxb3os double-knockout (DKO) mice. Compared to SKO, D..., Data were collected from experiments that were performed in mouse kidneys. Kidneys were harvested from mice at diffrerent age groups and processed for histological or molecular analysis, as described in the manuscript. All histological and molecular assessments were performed by experienced technicians who are blinded to the experimental group of the animal., All imaging data can be opened using the following programs: ImageJ, Adobe acrobat viewer, and Preview.
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