Prader-Willi Syndrome Animal Model Service

Protheragen's Prader-Willi syndrome animal model service provides researchers with a comprehensive suite of validated, preclinical models that faithfully recapitulate the complex genetic, metabolic, and behavioral hallmarks of the human condition. We offer fully customizable in vivo study designs, from model selection and breeding to detailed phenotypic characterization and efficacy testing, accelerating your therapeutic discovery and validation for Prader-Willi syndrome.

Overview of Prader-Willi Syndrome Animal Models

Prader-Willi syndrome is a genetic neurodevelopmental disorder caused by the absence of paternal gene expression from 15q11-q13. This genetic disorder is typified by growth delays, obesity, and excessive eating. This genetic complexity makes modeling the syndrome particularly challenging, yet critical for understanding its pathophysiology and developing effective therapeutics. Animal models are engineered to mimic specific genetic lesions found in human Prader-Willi syndrome, exhibit key phenotypes such as neonatal hypotonia, hyperphagia leading to severe obesity, hormonal dysregulation, cognitive impairments, and distinct behavioral patterns, providing a robust platform for preclinical investigation.

Fig.1 The efficacy of an EHMT2 inhibitor in a Prader-Willi syndrome mouse model. (Wang, S. E., et al., 2024)

Our Services

Leveraging our deep expertise in rare disease biology and advanced genetic engineering, we provide an integrated, end-to-end service that bridges the gap between basic research and application. Our team of scientists works collaboratively with you to select and develop the most appropriate model, design a rigorous study protocol, and generate high-quality, reproducible data that meets the stringent standards required for regulatory submissions, accelerate the progress of your Prader-Willi syndrome research and drug development project.

Animal Models of Prader-Willi Syndrome

Genetically Engineered Models

To support your Prader-Willi syndrome research, we provide a suite of genetically engineered models developed with cutting-edge technologies. Our portfolio includes well-validated models featuring targeted deletions of the Prader-Willi syndrome-critical region, Snord116 cluster, or Magel2 gene, all designed to meet your precise needs.

Optional models:

• Ndn ^tm1.1Mus model
• Magel2 ^tm1.1Mus model
• Magel2 ^tm1Stw model

• Snrpn ^tm2Cbr model
• Snord116 ^tm1.1Uta model
• Others

Snrpn-KO Mouse Model for Prader-Willi Syndrome Research

Case Study-Magel2 KO Mouse Model Development

Model Introduction

Designed to investigate the pathophysiology of Prader-Willi syndrome, the genetic cause of obesity, the Magel2 knockout (KO) mouse model targets a gene frequently deleted or mutated in this disorder. This model recapitulates key features of the syndrome, including impaired regulation of food intake and age-dependent weight gain, thereby providing a valuable in vivo system for studying metabolic and behavioral deficits in Prader-Willi syndrome and for evaluating potential therapeutic interventions.

Methodology

• Animal Model: A Magel2 KO mouse model was generated on a C57BL/6 background using genetic engineering techniques to disrupt the Magel2 gene, mimicking a common genetic abnormality observed in individuals with Prader-Willi syndrome.
• Phenotypic Analysis Methods: Comprehensive phenotypic analyses were conducted, with a focus on feeding behavior and metabolic parameters. In food deprivation/refeeding studies, mice were fasted for 24 hours and then provided with food; feeding behavior was recorded and analyzed during the first hour. Key parameters included total food intake, feeding latency, meal size, eating rate, and meal frequency. Locomotor activity and longitudinal body weight were also monitored under a standard diet.

Phenotypic Analysis & Results

Upon a 24-hour fast, male Magel2 KO mice exhibited a significant increase in food consumption upon refeeding compared to wild-type controls. Analysis of the meal pattern showed that this elevated food intake was driven by substantial increases in both meal size and meal duration, while the post-meal intervals remained unchanged, indicating a specific impairment in satiation signaling. In ad libitum feeding conditions, although daily intake remained comparable to controls, the Magel2 KO mice displayed notably reduced spontaneous locomotor activity. Furthermore, longitudinal assessment revealed that while body weights were indistinguishable during early development, Magel2 KO mice manifested a progressive, age-dependent weight gain, ultimately reaching approximately 15% greater body mass than wild-type counterparts by 25 weeks of age.

Fig.2 Satiation deficits and age-dependent weight gain in Magel2 KO mice. (A) Cumulative food intake was measured following a 24-hour fast and refeeding. (B-C) Average meal duration and meal size were analyzed during the refeeding period. (D) Spontaneous locomotor activity was assessed under free-feeding conditions. (E) Body weight progression was monitored in mice maintained on a standard diet. Data are presented as mean ± SEM (n=6; ***p < 0.001, *p < 0.05).

Conclusion

These findings confirm that the Magel2 KO mouse model successfully recapitulates key aspects of Prader-Willi syndrome, including hyperphagia due to impaired satiety and the development of late-onset obesity. This model offers a robust and reliable preclinical platform for validating the efficacy of novel therapeutics targeting the underlying mechanisms of Prader-Willi syndrome, underscoring its utility for comprehensive drug discovery and safety assessment.

Contact Us

Beyond model generation and phenotypic characterization, Protheragen offers comprehensive pharmacokinetics studies to understand your compound's absorption, distribution, metabolism, and excretion, as well as rigorous drug safety and toxicology evaluations. We are your dedicated partner in translating promising discoveries into viable therapeutic candidates for Prader-Willi syndrome. Contact us today to discuss your specific research objectives and how our Prader-Willi syndrome animal model services can advance your program.

Reference

1. Wang, Sung Eun et al. "Newly developed oral bioavailable EHMT2 inhibitor as a potential epigenetic therapy for Prader-Willi syndrome." Molecular therapy: the journal of the American Society of Gene Therapy 32.8 (2024): 2662-2675.

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