Polycystic Kidney Disease – ADPKD Mouse Model (Pkd1 KO)
Use the gold-standard research ADPKD mouse model to test the efficacy of your novel therapeutics for Polycystic Kidney Disease
ADPKD Mouse Model Key Characteristics
Autosomal dominant polycystic kidney disease (ADPKD) is characterized by the development of renal fluid-filled cysts, eventually leading to kidney failure. With a prevalence of 4 in 10.000, ADPKD is a relatively common genetic disorder. Mutations in the Pkd1 gene are associated with approximately 85% of ADPKD cases.
To support the preclinical development of new drugs and therapies for ADPKD, InnoSer offers a well-established, conditional, renal-specific Pkd1 knock-out (KO) ADPKD mouse model.Â
✓ The ADPKD mouse model is an inducible, kidney-specific Cre (lox,lox)-Pkd1 knock-out (KO) model.Â
✓ Conditional KO of the Pkd1 gene at specific time points results in three different models with different stages of disease progression.
✓ ADPKD mice show age-dependent, reproducible cyst formation and epithelial cell proliferation, similar to ADPKD patients.Â
✓ InnoSer offers multiple validated positive controls in the ADPKD mouse model.Â
Take advantage of InnoSer’s expertise, flexibility and collaborative approach for your research. We support our clients in identifying new drugs or applications, characterizing their pharmacological properties, and conducting safety and efficacy testing with state-of-the-art readout capabilities and histopathological analysis.Â
InnoSer’s neurology expert team possesses relevant experience in working with multiple therapy types ranging from small molecules, biologics (antibodies, peptides, enzymes), and gene therapy (viral vectors – e.g.. AAVs).Â
ADPKD Mouse Model Options
InnoSer offers different ADPKD mouse models by specifically timed Tamoxifen-induced Pkd1 knockout. There are three models available depending on which post-natal (P) day Tamoxifen is administered:Â
The P10 model is widely used as a first screening platform as it offers quick and robust results with renal cyst formation, while the P18 and P40 models show a slower progression even closer to clinical phenotypes.Â
For all your nephrology projects, we support custom in vivo models for kidney injury and toxicological studies.Â
| Model | Cyst characteristics |
| P10 | Quick progression of cyst formation in the distal segment of the nephron |
| P18 | Slow progression with cysts in all segments of the nephron |
| P40 | Slow and reproducible cyst formation in the proximal part of the nephron |
Timelines using ADPKD Mouse Model
Conditional Pkd1 knockout at different time points (P10, P18, P40) allows the establishment of multiple mouse models, with different disease progressions and phenotypes to meet your specific requirements in terms of study duration, outcome measures and clinical translatability.Â
ADPKD Mouse Model Sample Data
ADPKD mice show a progressive decrease in kidney function marked by a decrease in GFR.
Over time, we observe a significant decrease in the GFR of the ADPKD group in comparison to the healthy control group, confirming the loss of renal function in PKD mice and the suitability of this method in efficacy studies in this preclinical mouse model of ADPKD. Read more about including transdermal GFR in your nephrology studies here.Â
Cystic index enables the end-stage efficacy assessment of your test compound on renal health.
(A) Cystic index in the P10 model is significantly lower in the Everolimus and test compound A groups compared to the vehicle control group (mean ± SEM; one-way ANOVA). (B) Cystic Index in the P18 model is significantly lower in the Tolvaptan and test compound B groups compared to the vehicle control group (mean ± SEM; one-way ANOVA). Read more about the difference between the P10 and P18 models here.Â
Salsalate treatment (0.25% in food) reduces cystic index (%) in the ADPKD mouse model.
(A) Compared to Pkd1 KO mice administered with vehicle (food pellets), Salsalate-administered Pkd1 KO mice show a significant decrease in cystic index (P=0.0001), indicative of improvement of the pathophysiological kidney disease. (B) Representative histological image of kidney obtained from healthy mouse. (C) Representative histological image of kidney obtained from Pkd1 KO vehicle-treated mouse. (D) Representative histological image of kidney obtained from Pkd1 KO Salsalate-treated animal. In comparison to vehicle-treated animals, Salsalate-treated mouse have smaller cysts with lower distribution (arrows). View more validation data using Salsalate as a positive control here.Â
ADPKD Mouse Model Readouts
Histopathology readouts
Histopathology assessments performed by certified veterinary pathologists:
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- Baseline spectral analyses of ECoG data Cystic index and associated pathological lesionsÂ
- Special stainings and immunohistochemistry for specific markers of interest
Featured Publications
- Dagorn, P. G., Buchholz, B., Kraus, A., Batchuluun, B., Bange, H., Blockken, L., Steinberg, G. R., Moller, D. E., & Hallakou-Bozec, S. (2023). A novel direct adenosine monophosphate kinase activator ameliorates disease progression in preclinical models of Autosomal Dominant Polycystic Kidney Disease. Kidney International, 103(5), 917–929. https://doi.org/10.1016/j.kint.2023.01.026
- Brownjohn, P. W., Zoufir, A., O’Donovan, D. J., Sudhahar, S., Syme, A., Huckvale, R., Porter, J. R., Bange, H., Brennan, J., & Thompson, N. T. (2024). Computational drug discovery approaches identify mebendazole as a candidate treatment for autosomal dominant polycystic kidney disease. Frontiers in pharmacology, 15, 1397864. https://doi.org/10.3389/fphar.2024.1397864
Your Nephrology Research with InnoSer
Powered by ultrasound
In vivo imaging has become a valuable tool for collecting mid study data particularly in long term animal studies. These non-invasive methods can be applied with high sensitivity and in real time. With InnoSer’s imaging capabilities, track your lead compound effects on cyst growth easily. Read more >>
Smart pathological assessment
Histopathological assessments are standard parts of our ADPKD model readouts. Thanks to smart algorithms being trained to identify cysts in an automated manner, these can be offered in an efficient way, also with possibilities of long term and secure cloud storage of the images. Read more >>
Scientific experts to guide you
An expert team of scientists with vast experience in our ADPKD model helps you choose the right model options and set up optimal study designs for your nephrology projects. Curating the preclinical testing of your lead compounds with a deep understanding in the field is your solution to accelarating your drug development.
Your ADPKD Research Starts Here.
Access detailed study timelines, essential readouts, and robust validation data.
The People Behind Your Research
The ADPKD Mouse Model was Developed by Prof. Dr. Dorien Peters of the LUMC
Dr. Peters from Leiden University Medical Center (LUMC) focuses on insights into the genetic, pathophysiologic, and functional mechanisms of inherited disorders.
Laura Blockken, Nephrology Study Director
An expert team of scientists with vast experience in our ADPKD mouse model help you choose the right model and set up your optimal study design. We provide the solution to accelerating your drug development.
Frequently Asked Questions
What is the mouse model of ADPKD?
The mouse model of ADPKD is a genetically engineered research tool used to study Autosomal Dominant Polycystic Kidney Disease (ADPKD). InnoSer’s inducible kidney-specific Cre(lox,lox)–Pkd1 knockout (KO) mouse model is the gold standard model for evaluating the efficacy of novel therapeutics for ADPKD in preclinical research. Discover how this model has been used in research. View the publication list here.Â
What positive controls are used in the ADPKD mouse model?
Positive controls in the ADPKD mouse models include known compounds that predictably influence cyst formation. Including positive controls in a study is essential to establish a comparison for evaluating the efficacy of novel therapeutic compounds. At InnoSer, we have validated a multitude of positive controls: – mTOR inhibitors (Everolimus, Rapamycin) – Vasopressin receptor antagonists (Mozavaptan, Tolvaptan; only approved ADPKD treatment), – AMPK activators (Salsalate; view validation data in our previous blog posts here and here). The selection of a positive control depends on your test item’s mechanism of action. For example, Salsalate may be used as comparator for therapies targeting AMPK-involved pathways. Contact our team to identify the right positive controls for your ADPKD study.
How do your models replicate the cyst formation seen in ADPKD patients?
InnoSer’s Pkd1 knockout mouse models of ADPKD highlight different aspects of cyst formation observed in human ADPKD patients by conditionally disrupting the Pkd1 gene expression. The inducible feature of this model allows a disruption of Pkd1 gene expression at specifically chosen time points, both in juvenile and adult mice. This not only allows a well-controlled evaluation of ADPKD pathogenesis, but also the creation of different ADPKD progression models (P10, P18, and P40), thanks to the characteristic age-dependent cyst formation observed in these animals. This allows the evaluation of different aspects of disease progression and how they can be influenced by a therapeutic test item depending on the mode of action. The different models all replicate hallmark features of human ADPKD, including progressive kidney enlargement, cyst formation, and impaired kidney function. Learn more about our P10, P18, and P40 models in our blog post here.
Are InnoSer's ADPKD mice readily available for studies?
Yes, InnoSer maintains a continuous stock of ADPKD mouse colonies, meaning that they do not have to be sourced from other laboratories, supporting quick study starts, whilst helping you avoid high costs associated with animal purchases as well as timeline delays due to quarantining periods. At InnoSer, we can accommodate studies with up to 8 treatment groups and handle >100 animals per study, ensuring flexibility for even the most complex study designs. Request a tailored study quote from our team today.
Does InnoSer have capability to run other studies in other nephrology-related models?
- Systemic Lupus Erythematosus (SLE).
- Diabetic Kidney Disease.
- Kidney ischemia-reperfusion injury.
- Glomerular nephritis models.
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Therapeutic targets for ADPKD
In ADPKD, mutations in the PKD1 or PKD2 gene cause changes in polycystin 1 or 2 (PC1 and PC2) expression, which in turn interferes with several intracellular signaling pathways that are e.g., involved in cell proliferation, fluid secretion, and ciliary function. The...
Glomerular filtration rate (GFR) in the ADPKD mouse model
Preclinical studies aiming to assess kidney function traditionally include readouts such as serum creatinine and/or blood urea nitrogen (BUN). However, the use of readouts that are more clinically relevant such as glomerular filtration rate (GFR) is highly encouraged,...
Effect of Salsalate on disease progression in the ADPKD Mouse ModelÂ
Salsalate is a pro-drug dimer of salicylate belonging to the family of NSAIDs, activating AMPK through direct interactions with the drug-binding domain of the AMPK beta-1 isoform. As such, Salsalate arises as a key candidate for drug repurposing in ADPKD.  To...
Salsalate ameliorates disease progression in ADPKD mouse model
In this newsletter we present in-house validation data of Salsalate on disease progression in the ADPKD mouse model. One of key therapeutic strategies undertaken to provide new and efficacious treatments for ADPKD is targeting key signaling pathways that drive cystic...
AAALAC Accreditation
InnoSer has earned the AAALAC accreditation, demonstrating our commitment to responsible animal care and use. AAALAC International is a nonprofit organization that promotes the humane treatment of animals in science through voluntary accreditation and assessment programs. Our accreditation is valid for three years, incl. 2023. Read more about the AAALAC accreditation programme here.
Animal Welfare
The 3Rs impact everything from policy and regulatory change to the development and uptake of new technologies and approaches. This is why InnoSer has ongoing commitment and monitoring of these processes. The steps we practice maximize our ability to replace, reduce and refine animal involvement and facilitate our commitment to these principles when it comes to research and drug development.
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