It is well-established that ADPKD shows heterogeneous disease onset and progression in patients, necessitating preclinical models that capture the heterogeneous disease penetration observed in patients.  

Therefore, new datasets in our adult-onset (also referred to as the P40 mouse model) further expand our existing ADPKD platform (namely, our P10 and P18 mouse models; see comparison table below) with a mouse model that offers extended therapeutic dosing windows, making it suitable for disease prevention and biomarker identification studies, as well as for long-term assessment of treatment efficacy and potential adverse effects of novel ADPKD therapeutics. 

KO of Pkd1 at PND40 results in progressive renal enlargement in the CrePkd1lox,lox mouse model  

KO of Pkd1 via tamoxifen dosing at PND40 in the Cre;Pkd1^lox,lox mouse model (Lattinga-van Leeuwen et al., 2007) results in a controlled adult-onset disease induction, leading to progressive renal enlargement and cyst-driven kidney expansion over time, as captured non-invasively by ultrasound imaging (Figure 1). The strong correlation between kidney volume assessed via ultrasound and kidney weight corrected for body weight highlights the relevance in early detection of disease progression and monitoring of treatment effects as a non-invasive intermediate readout. 

FIGURE 1. Longitudinal assessment of kidney volume via ultrasound imaging reveals progressive kidney enlargement in the P40 mouse model. (A-B) Progressive renal enlargement in tamoxifen-induced Pkd1 cKO mice compared to controls. (C) Correlation analysis between kidney volume assessed via ultrasound and terminal kidney weight corrected for body weight. Data shown as M±SEM. 

Blood urea nitrogen (BUN) confirms development of end-stage renal dysfunction in Pkd1 KO at PND40 in ADPKD mice 

FIGURE 3. Blood urea nitrogen (BUN) confirms the development of progressive renal dysfunction in the P40 mouse model. (A) Tamoxifen-induced Pkd1 cKO mice exhibit elevated blood urea nitrogen (BUN) levels at end-stage disease compared with uninduced littermate controls, consistent with progressive loss of renal function. (B) Terminal increases in BUN provide a functional readout of renal impairment, reflecting reduced glomerular filtration capacity in late-stage ADPKD and complementing structural endpoints such as kidney enlargement and cyst burden. (C) Correlation between BUN and kidney weight/BW demonstrates that BUN reflects disease progression, serving as a quantitative non-invasive blood biomarker , particularly in ADPKD mice with advanced structural disease burden, complementing imaging endpoints. Data shown as M±SEM. 

KO of Pkd1 at PND40 leads to progressive cyst formation and kidney enlargement in ADPKD mice 

FIGURE 3. Progressive cyst formation and kidney enlargement in P40 mice. (A) H&E-stained kidneys from tamoxifen induced mice were collected at baseline (PND49), early (PND84), intermediate (PND119), late (PND145), and terminal (PND180) stages (images scaled to same size). Example kidney image from uninduced littermates obtained at same timepoints (image shown from kidney isolated at baseline) were included as a control. (B) Cystic index quantifications confirm progressive increase in cysts in P40 mice. 

Compare & contrast InnoSer’s ADPKD mouse models: Which mouse model is the most suitable for your research?

In this newsletter, we have presented data showing that the P40 ADPKD mouse model develops progressive kidney enlargement, functional decline, and cyst formation over time. Complementing our P10 and P18 mouse models, representing the industry gold standard ADPKD mouse models, frequently used across multiple compound lead screening and preclinical efficacy studies due to their rapid disease phenotype, the P40 mouse model offers you the possibility to perform long-term studies in a comparable ADPKD phenotype setting. 

TABLE 1. Key differences between different ADPKD model subtypes

Interested in performing efficacy studies using InnoSer’s ADPKD mouse models? Consulting with our nephrology study experts will allow you to carry out tailored studies while collecting the most study-appropriate data. We also advise you on the most optimal model selection and study design set-up, considering your budget and study timelines to enable you with the most cost-effective solution without sacrificing any important research insights.