Data from: Ablation of Hoxb3os in mouse polycystic kidney disease exacerbates cystogenesis

<p>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, <em>PKD1</em> and <em>PKD2</em>. In this study, we investigated the role of the long noncoding RNA (lncRNA) <em>Hoxb3os</em> in ADPKD by ablating its expression in the mouse. <em>Hoxb3os</em>-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 <em>Hoxb3os</em> in cystogenesis, we crossed the <em>Hoxb3os</em>-null mouse to two orthologous <em>Pkd1</em> mouse models: <em>Pkhd1/Cre</em>;<em>Pkd1^F/F</em> (rapid cyst progression) and <em>Pkd1^RC/RC</em> (slow cyst progression). Ablation of <em>Hoxb3os</em> exacerbated cyst growth in both models. To gain insight into the mechanism whereby <em>Hoxb3os</em> inhibition promotes cystogenesis, we performed proteomic analysis of mTOR/Akt pathway between <em>Pkd1</em> single-knockout (SKO) and <em>Pkd1-Hoxb3os</em> double-knockout (DKO) mice. Compared to SKO, DKO mice presented with enhanced levels of total and phosphorylated Rictor. This was accompanied by increased phosphorylation of Akt^Ser473, a known mTORC2 effector site. Physiologically, kidneys from DKO mice displayed between 40-50% increase in cell proliferation. Results from this study indicated that ablation of <em>Hoxb3os</em> in mouse PKD exacerbated cystogenesis and dysregulated mTORC2.</p>