Autosomal dominant polycystic kidney disease (ADPKD) shows heterogeneous disease onset and progression in patients, demanding preclinical models that capture the full natural history of the condition. Presented at the 8th CKD Drug Development Summit in Boston (2026), this poster from our nephrology team presents comprehensive longitudinal characterization of an adult-onset ADPKD mouse model induced by Pkd1 knockout at postnatal day 40 (P40). 

このモデルは、生存期間が約28週間であり、超音波による腎臓の進行性肥大、血中尿素窒素（BUN）による腎機能障害、および組織病理学的検査による嚢胞性疾患の進行を、非侵襲的にモニタリングすることが可能です。 確立されたP10およびP18誘導モデルと比較して、P40モデルは治療の適用期間を大幅に延長しており、疾患予防研究、バイオマーカーの同定、および新規ADPKD治療薬の長期有効性評価に非常に適しています。

Autosomal dominant polycystic kidney disease (ADPKD) shows heterogeneous disease onset and progression in patients, necessitating preclinical models capturing this variability. While early postnatal Pkd1 inactivation models (PND10 and PND18) are widely used for efficacy studies due to rapid phenotype induction, adult-onset models with a more progressive disease course provide a complementary platform for biomarker identification and extended therapeutic evaluation before the onset of significant kidney function decline. 

Pkd1 knockout was induced at PND40 (P40) in the Cre;Pkd1lox,lox mouse model. PKD progression was assessed at baseline (PND49), early (PND84), intermediate (PND119), late (PND146), and terminal (PND180) timepoints via kidney volume by ultrasound, blood urea nitrogen (BUN), and H&E histopathology. 

Progressive renal enlargement was confirmed by longitudinal ultrasound, with strong correlation between kidney volume and kidney weight/body weight (R²=0.8551). BUN was consistently elevated in tamoxifen-induced Pkd1 cKO mice versus uninduced littermate controls, with BUN correlating with kidney weight/body weight (R²=0.7603). Histological analysis demonstrated progressive cyst formation from baseline through terminal stages, with proximal tubule involvement predominating in the P40 model. 

The P40 ADPKD mouse model provides an extended in vivo phase of approximately 28 weeks, suitable for disease prevention studies, biomarker identification, longitudinal efficacy assessment, and evaluation of adverse effects. The InnoSer ADPKD platform — spanning P10, P18, and P40 induction variants — models the heterogeneous ADPKD patient population across different disease stages.