In Vivo Model Development for Fibrodysplasia Ossificans Progressiva

Protheragen offers comprehensive in vivo animal model development services specifically tailored for Fibrodysplasia Ossificans Progressiva (FOP). Our robust portfolio of mouse models supports the preclinical evaluation of novel therapeutics, providing scientifically validated platforms for understanding disease mechanisms and assessing treatment efficacy in FOP.

Fibrodysplasia Ossificans Progressiva (FOP) is an ultra-rare genetic disorder characterized by progressive heterotopic ossification, leading to severe immobility and morbidity. Animal models, particularly genetically engineered and injury-induced mouse models, are indispensable for elucidating FOP pathogenesis and testing therapeutic interventions. At Protheragen, we utilize Mus musculus (mouse), primarily the C57BL/6 strain and various genetically modified backgrounds, to closely mimic the genetic and pathological features of human FOP. Our models incorporate clinically relevant mutations in the ACVR1 gene, which is central to FOP, ensuring translational relevance for drug discovery and mechanistic studies.

Genetic Models

Genetic models are developed by introducing specific mutations or transgenes associated with FOP, such as ACVR1 knockin or transgenic constructs, into the mouse genome. These models faithfully recapitulate the genetic etiology of human FOP, allowing for the study of disease onset, progression, and the evaluation of targeted therapies. Key advantages include stable inheritance of the disease phenotype, reproducibility, and the ability to model both constitutive and tissue-specific gene expression. Primary research applications include mechanistic studies, target validation, and preclinical efficacy testing of small molecules or biologics targeting ACVR1 signaling.

Chemically-Induced Models

Chemically-induced models employ biological agents, such as cardiotoxin, to trigger localized muscle injury and stimulate heterotopic ossification in genetically susceptible mice (e.g., conditional ACVR1 transgenics). This approach allows for controlled induction of disease flares and enables the study of injury-related exacerbation of FOP. Advantages include temporal control over disease induction and the ability to assess therapeutic interventions in the context of acute or chronic injury. These models are particularly useful for evaluating anti-inflammatory and anti-fibrotic agents, as well as elucidating the interplay between injury, inflammation, and ectopic bone formation.

Mechanically-Induced Models

Mechanically-induced models involve the application of physical injury, such as pinch or mechanical trauma, to initiate heterotopic ossification in genetically predisposed mice. These models simulate the effects of minor trauma, a known trigger for FOP flare-ups in patients. The main advantages are the reproducibility of injury and the ability to study the effects of mechanical stress on disease progression. Research applications include the assessment of prophylactic and therapeutic interventions following trauma, and the investigation of tissue repair and ossification pathways.

Protheragen delivers a complete solution for FOP animal model development, including model selection, custom generation, in vivo study design, and comprehensive data analysis. Our service encompasses induction of disease (genetic, chemical, or mechanical), longitudinal monitoring, and endpoint assessments. Key efficacy endpoints include radiographic imaging (micro-CT), histopathological evaluation, quantification of heterotopic bone formation, biomarker analysis, and functional assessment of mobility. Our analytical capabilities extend to molecular profiling (qPCR, Western blot, immunohistochemistry), advanced imaging, and customized readouts tailored to client needs. Rigorous quality control measures are implemented at every stage, from genetic validation to reproducibility testing and data integrity assurance, ensuring reliable and translatable results.

Partnering with Protheragen provides access to state-of-the-art FOP animal models, expert scientific support, and tailored preclinical study solutions that accelerate your therapeutic development pipeline. Our commitment to scientific excellence, robust quality standards, and collaborative approach ensures that your research objectives are met with precision and confidence. Contact us today to discuss your FOP model requirements and advance your drug discovery program with Protheragen.