In Vivo Model Development for Cystic Fibrosis

Protheragen offers a comprehensive suite of in vivo animal model development services specifically tailored for Cystic Fibrosis (CF) research. Leveraging a diverse portfolio of genetically engineered, chemically induced, and infection-based models across multiple species, we empower our clients to advance therapeutic discovery, efficacy testing, and mechanistic studies for CF. Our expert team provides end-to-end support, from model selection and establishment to data analysis, ensuring scientifically robust and translationally relevant outcomes.

Cystic Fibrosis is a complex, multisystem genetic disorder caused primarily by mutations in the CFTR gene, leading to chronic respiratory and gastrointestinal symptoms. Animal models are indispensable in CF research, as they provide critical insights into disease mechanisms, progression, and therapeutic responses. At Protheragen, we utilize a wide array of species—including zebrafish (Danio rerio), mice (Mus musculus) of various strains (e.g., C57BL/6, FVB, Balb/c), rats (Rattus norvegicus), ferrets (Mustela putorius), pigs (Sus scrofa), rabbits (Oryctolagus cuniculus), and sheep (Ovis aries). These models recapitulate key aspects of human CF pathology, such as CFTR dysfunction, mucus accumulation, infection susceptibility, and inflammation, providing a robust platform for preclinical evaluation of novel interventions.

Genetic Models

Genetic models involve the targeted modification of genes implicated in Cystic Fibrosis, most notably CFTR. Methodologies include gene knockout (complete inactivation), mutation knock-in (e.g., F508del), conditional or tissue-specific mutations, and transgenic overexpression. These models are developed using advanced genetic engineering techniques such as CRISPR/Cas9, homologous recombination, or transgenesis. Advantages include high fidelity to human CF mutations, reproducible phenotype expression, and suitability for mechanistic and therapeutic studies. Applications encompass pathophysiology research, drug efficacy and safety testing, gene therapy evaluation, and biomarker discovery.

Infection-Induced Models

Infection-induced models simulate the chronic airway infections and inflammation characteristic of CF by introducing bacterial (e.g., Pseudomonas aeruginosa), fungal, or human microbiota agents into the respiratory tract of animals. These models can be established in both wild-type and CFTR-deficient backgrounds to study host-pathogen interactions and immune responses. Key advantages include the ability to mimic disease exacerbations, assess antimicrobial therapies, and investigate the impact of infection on CF progression. Primary applications include anti-infective drug testing, immunomodulatory therapy assessment, and microbiome research.

Chemically-Induced Models

Chemically-induced models use pharmacological agents such as CFTR inhibitors (e.g., CFTRinh-172), TGF-beta1, or human neutrophil elastase to transiently replicate CF-like dysfunction in animal airways or tissues. These models are established by administering the chemical agent systemically or locally, resulting in reversible CFTR impairment or enhanced mucus production. Advantages include rapid induction, cost-effectiveness, and the ability to model specific disease components without genetic manipulation. They are particularly useful for high-throughput drug screening, acute intervention studies, and evaluating airway physiology.

Transgenic Models Expressing Human Genes

Transgenic models expressing human CFTR or related genes are developed by introducing human gene constructs into animal genomes. These models enable the study of human-specific gene function, mutation effects, and cross-species therapeutic responses. The methodology involves microinjection or viral-mediated gene transfer. Advantages include direct translational relevance and the ability to test human-targeted therapies. Applications range from gene editing and replacement therapy research to validation of humanized drug candidates.

Protheragen provides a complete solution for in vivo Cystic Fibrosis model development and study execution. Our service encompasses model design and customization, animal procurement and husbandry, genetic or chemical induction, infection protocols, and comprehensive endpoint analysis. Key efficacy endpoints include survival, body weight, airway and intestinal physiology, mucus production, lung function (e.g., spirometry, plethysmography), histopathology, inflammatory markers, microbial load, and CFTR activity (chloride transport assays). Our analytical capabilities span molecular biology (PCR, Western blot, ELISA), imaging (micro-CT, confocal microscopy), microbiology, and advanced biostatistics. Rigorous quality control is maintained through genotyping, phenotype validation, standardized protocols, and compliance with ethical guidelines, ensuring reproducibility and data integrity.

Partnering with Protheragen gives you access to deep expertise, a broad spectrum of validated CF animal models, and state-of-the-art analytical platforms, all tailored to accelerate your Cystic Fibrosis research and therapeutic development. Our collaborative approach, scientific rigor, and commitment to quality ensure that your studies yield actionable, translatable results. Contact us today to discuss your project needs and discover how our in vivo CF model services can advance your research objectives.