In Vivo Model Development for Primary Sclerosing Cholangitis

Protheragen offers comprehensive in vivo model development services for Primary Sclerosing Cholangitis (PSC), supporting preclinical research and therapeutic discovery. Our suite of animal models is meticulously designed to recapitulate the pathophysiological features of PSC, enabling our clients to evaluate the efficacy and safety of novel treatments in translationally relevant systems.

Primary Sclerosing Cholangitis is a chronic, progressive liver disease characterized by inflammation and fibrosis of the bile ducts, often leading to liver failure. Due to the complex and multifactorial nature of PSC, robust animal models are essential for elucidating disease mechanisms and testing potential therapies. Protheragen employs both mouse (Mus musculus) and rat (Rattus norvegicus) models, utilizing a variety of strains such as Balb/cJ, C57BL/6, FVB/N, NOD/LtJ, and Sprague Dawley. These models—ranging from genetic knockouts to chemically-induced and surgically manipulated systems—closely mirror the human disease, providing valuable platforms for translational research and drug development.

Genetic Models

Genetic models involve the targeted knockout or conditional knockout of genes implicated in PSC pathogenesis, such as the Abcb4 gene. These models are typically developed in mouse strains like Balb/cJ and FVB/N, as well as hybrid backgrounds (e.g., FVB/N x NOD/LtJ). The methodology includes gene editing techniques to disrupt the function of key transporters, leading to spontaneous development of cholangitis and biliary fibrosis. Key advantages include high reproducibility, well-characterized disease progression, and the ability to study genetic contributions to PSC. These models are invaluable for mechanistic studies, biomarker discovery, and preclinical testing of gene-targeted therapies.

Chemically-Induced Models

Chemically-induced models utilize hepatotoxic agents such as 3,5-diethoxycarbony1-1,4-dihydrocollidine (DDC), dextran sulfate, or alpha-naphthylisothiocyanate to induce cholangitis and liver fibrosis in mice (primarily C57BL/6 and FVB/N strains) and rats (Sprague Dawley). The methodology involves administering these agents via diet or injection, resulting in bile duct injury, periductal fibrosis, and immune cell infiltration that mimic key aspects of PSC. Advantages include rapid disease induction, dose-dependent severity, and suitability for high-throughput screening. These models are widely used for evaluating anti-fibrotic, anti-inflammatory, and immunomodulatory therapies.

Surgical and Infection-Induced Models

This category includes models such as bile duct ligation (BDL) in rats and viral infection-induced cholangitis in genetically susceptible mice. BDL involves surgically obstructing the common bile duct in Sprague Dawley rats, leading to cholestasis, ductal proliferation, and fibrosis. Viral infection models combine genetic susceptibility (e.g., Abcb4 knockout) with exposure to hepatotropic viruses, recapitulating the interplay between genetic and environmental factors in PSC. These models offer the advantage of closely simulating the obstructive and infectious components of human PSC, making them ideal for studying disease progression, host-pathogen interactions, and testing regenerative therapies.

Protheragen delivers a full-spectrum PSC animal model service, encompassing model selection, establishment, and customized study design. Our offering includes: precise genetic engineering and validation, controlled chemical or surgical induction, and comprehensive animal care. Key efficacy endpoints measured include liver function tests (ALT, AST, ALP, bilirubin), histopathological assessment of fibrosis and inflammation, immunohistochemistry, bile acid profiling, and survival analysis. Our advanced analytical capabilities cover molecular biology assays (qPCR, Western blot), cytokine profiling, and next-generation sequencing. Rigorous quality control is maintained through standardized protocols, validated endpoints, and continuous monitoring to ensure data integrity and reproducibility.

By partnering with Protheragen, clients benefit from our scientific expertise, state-of-the-art facilities, and commitment to delivering reliable, translatable results. Our tailored animal model solutions accelerate the path from discovery to clinic, helping you overcome the challenges of PSC research and drug development. Contact us today to discuss how our in vivo PSC model services can empower your next breakthrough.