Peutz-Jeghers syndrome animal models are preclinical research tools that recapitulate key pathological features of human Peutz-Jeghers syndrome, including gastrointestinal hamartomatous polyps and increased cancer risk. Protheragen provides specialized, custom-developed Peutz-Jeghers syndrome animal models to support preclinical research and therapeutic discovery. With end-to-end solutions, from model generation and phenotypic validation to drug efficacy testing, we empower researchers to accelerate translational studies for this rare genetic disorder.

Introduction to Peutz-Jeghers Syndrome Animal Models

Peutz-Jeghers syndrome is caused by inactivating mutations in the STK11/LKB1 gene and is an autosomal dominant disorder. The animal models designed to simulate the pathogenesis of human Peutz-Jeghers syndrome allow for the study of the mechanism of the disease, including polyp progression and metastasizing potential. They are invaluable in the biologically relevant evaluation of new therapeutics, potential disease biomarkers, and strategies aimed at disease therapy.

Fig.1 CTF-specific loss of Stk11 induces polyposis. (Domènech-Moreno, E., et al., 2025)

Methods of Peutz-Jeghers Syndrome Animal Model Development

Developing animal models for Peutz-Jeghers syndrome primarily relies on the targeted disruption of the Lkb1 (STK11) gene in mice to simulate the human genetic disorder. This is done using advanced genetic engineering methods, specifically homologous recombination in embryonic stem cells, to generate constitutive or conditional knockout alleles.

The resulting models are rigorously phenotyped through histopathological analysis to confirm the hallmark development of hamartomatous polyps and monitored for the progression to adenocarcinomas, thus providing an essential in vivo system for studying the pathogenesis and potential therapeutics of the syndrome.

Our Services

With decades of experience in modeling rare gastrointestinal diseases, cutting-edge genome editing, and detailed phenotypic descriptions, Protheragen provides highly reproducible and relevant development services for Peutz-Jeghers syndrome animal models. We offer custom model generation, histopathological services, and molecular profiling to meet diverse research needs, from mechanistic studies, therapy development, to preclinical investigations.

Animal Models of Peutz-Jeghers Syndrome

Genetically Engineering Model

We provide genetically engineered models that accurately recreate tissue-specific pathogenesis for Peutz-Jeghers syndrome. These models enable precise manipulation of the Lkb1 gene and facilitate the exploration of polyp initiation, progression, and tumorigenesis within a controlled, immunocompetent setting.

• Lkb1^+/- model
• And more

• Lkb1-cKO (Stk11-cKO) model

Stk11-cKO Mouse for Peutz-Jeghers Syndrome Research

Case Study: Lkb1^+/- Mouse Model

Model Introduction

Utilizing a genetically engineered mouse model with heterozygous loss of the Lkb1 gene (also known as Stk11), this study recapitulates key gastrointestinal manifestations of Peutz-Jeghers syndrome, including the development of intestinal polyps. The model serves as a robust preclinical tool for investigating disease mechanisms and evaluating novel therapeutic strategies aimed at suppressing gastrointestinal tumorigenesis.

Methodology

• Animal Model: The Lkb1^+/- mouse model was established on a C57BL/6 background to mimic the genetic predisposition observed in human Peutz-Jeghers syndrome. Animals were maintained under specific pathogen-free conditions. At 9 months of age, corresponding to the average onset of polyposis, Lkb1^+/- mice received anti-IL-17A blocking antibody administration once every three days until reaching 12 months of age. Age-matched control groups were treated with immunoglobulin G (IgG) on the same schedule.
• Phenotypic Analysis Methods: Polyp progression was assessed through systematic quantification of polyp size, number, and histology. Following a 24-hour fixation in 10% neutral-buffered formalin, intestinal tissues were processed for paraffin embedding. Subsequent histological examination included hematoxylin and eosin (H&E) staining for structural evaluation and immunohistochemistry for biomarker analysis.

Phenotypic Analysis & Results

Initiating anti-IL-17A antibody therapy in Lkb1^+/- mice at 9 months of age significantly suppressed polyp development, resulting in an approximately 3-fold reduction in polyp size compared to the IgG control group (Fig. 2B). These data demonstrate that in vivo IL-17A blockade is an effective therapeutic strategy for suppressing gastrointestinal tumor growth in this established model of Peutz-Jeghers syndrome.

Fig.2 IL-17 blockade attenuates GI tumorigenesis in Lkb1^+/- mice. (A) Therapy schedule. (B) Reduced polyp area after anti-IL-17A therapy. Data are presented as mean ± SEM (n=5; *p < 0.05)

Conclusion

These findings validate the Lkb1^+/- mouse as a highly relevant model for studying Peutz-Jeghers syndrome pathogenesis and therapeutic interventions. The marked suppression of polyp growth following IL-17A blockade highlights the potential of immunomodulatory strategies for treating PJS-related gastrointestinal neoplasia. This model system offers a reliable platform for preclinical evaluation of drug candidates targeting inflammation and tumor development in Peutz-Jeghers syndrome.

Contact Us

From model development and validation to extensive drug testing, Protheragen's integrated platform provides powerful support for your Peutz-Jeghers syndrome research programs. We also provide pharmacokinetic studies, toxicity assessments, efficacy evaluations, and biomarker analysis services. Partner with us to advance your therapeutic candidates from discovery to preclinical research. Contact our team to discuss your project requirements and receive a customized solution.

Reference

• Domènech-Moreno, Eva et al. "Interleukin-11 expressed in the polyp-enriched fibroblast subset is a potential therapeutic target in Peutz-Jeghers syndrome." The Journal of Pathology 266.1 (2025): 66-80.

All of our services and products are intended for preclinical research use only and cannot be used to diagnose, treat or manage patients.