In Vivo Model Development for Pik3Ca Related Overgrowth Spectrum

Protheragen offers comprehensive in vivo animal model development services tailored to the study and therapeutic evaluation of Pik3Ca Related Overgrowth Spectrum (PROS). Our specialized platforms enable the creation and application of scientifically validated models that closely recapitulate the genetic and phenotypic features of PROS, empowering researchers and pharmaceutical partners to advance preclinical testing of novel interventions.

Pik3Ca Related Overgrowth Spectrum encompasses a group of rare disorders caused by somatic mutations in the PIK3CA gene, leading to abnormal tissue growth and mosaic overgrowth syndromes. Accurate animal models are essential for elucidating disease mechanisms and evaluating potential therapies. At Protheragen, we employ Mus musculus (mouse) as the primary species, leveraging conditional transgenic strains that express human-relevant PIK3CA mutations. These genetically engineered models faithfully mirror the pathophysiology observed in human PROS, making them invaluable for translational research and the preclinical assessment of therapeutic candidates.

Genetic Models

Genetic models are established through the introduction of disease-relevant mutations into the mouse genome, most notably using conditional transgenic strategies to express mutant PIK3CA alleles in a tissue-specific or inducible manner. This approach allows precise control over mutation timing and localization, closely mimicking the mosaic nature of PROS in patients. Key advantages include high fidelity to human disease genetics, reproducibility, and the capacity to study both developmental and adult-onset phenotypes. These models are primarily used for investigating disease mechanisms, validating genetic targets, and evaluating gene or small molecule therapies.

Chemically-Induced Models

Chemically-induced models involve the administration of specific compounds that activate or mimic PI3K pathway dysregulation in vivo. While not as genetically precise as transgenic models, this methodology enables rapid induction of overgrowth phenotypes and can be used to screen for pathway modulators. Advantages include scalability, cost-effectiveness, and suitability for high-throughput drug testing. These models are best suited for early-stage pharmacological screening and proof-of-concept studies targeting the PI3K/AKT/mTOR axis.

Cell Transplantation Models

Cell transplantation models are developed by engrafting cells harboring PIK3CA mutations (engineered ex vivo) into immunocompromised mice. This strategy allows the study of human or mouse mutant cell behavior in a controlled in vivo environment, facilitating the investigation of cell-autonomous and microenvironmental interactions. Advantages include the ability to assess human-specific mutations and test cell-based therapies. Applications include in vivo validation of gene editing, cell therapy approaches, and evaluation of tumorigenic potential.

Protheragen delivers a complete, customizable solution for in vivo PROS model development and utilization. Our service encompasses model design, generation, validation, and comprehensive phenotypic and therapeutic testing. Key efficacy endpoints include assessment of tissue and organ overgrowth, histopathological analysis, molecular profiling (PI3K/AKT/mTOR pathway activity), imaging (MRI, CT), and functional outcome measures. Our analytical capabilities extend to next-generation sequencing, quantitative PCR, western blotting, immunohistochemistry, and in vivo imaging. Stringent quality control is maintained through genotyping, phenotypic validation, and standardized protocols, ensuring data reliability and reproducibility throughout the study lifecycle.

Partnering with Protheragen provides access to cutting-edge animal models and expert scientific support, accelerating your PROS research and therapeutic development. Our integrated approach ensures robust, clinically relevant data and streamlines the path from discovery to preclinical validation. Contact us today to discuss your specific research needs and learn how our animal model services can drive your project forward.