In Vivo Model Development for Primary Biliary Cholangitis

Protheragen is dedicated to advancing Primary Biliary Cholangitis (PBC) research by offering a comprehensive suite of in vivo animal model development services. Our robust portfolio of validated PBC models enables pharmaceutical and academic partners to evaluate the efficacy, safety, and mechanisms of novel therapeutic candidates in settings that closely mimic human disease.

Primary Biliary Cholangitis is a chronic autoimmune liver disease characterized by progressive destruction of intrahepatic bile ducts, leading to cholestasis and, ultimately, liver failure. Animal models are indispensable for understanding PBC pathogenesis and for preclinical assessment of therapeutic interventions. At Protheragen, we employ a range of mouse and rat models—including genetically modified, chemically induced, and surgically induced strains such as C57BL/6, B6.129P2-Nfe2l2/MymRbrc, FVB.129P2-Abcb4tm1Bor/J, and Wistar rats—to recapitulate the complex immunopathology and fibrotic progression observed in human PBC. These models provide translational relevance and predictive value for human therapeutic outcomes.

Chemically-Induced Models

Chemically-induced models utilize agents such as 2-octynoic acid, polycytidylic-polyinosinic acid, and 3,5-diethoxycarbony1-1,4-dihydrocollidine to trigger cholangitis and fibrosis in rodents. These chemicals are administered via injection or dietary supplementation to induce immune-mediated bile duct injury and inflammation. Key advantages include reproducibility, rapid onset of pathology, and the ability to modulate disease severity by adjusting dosing regimens. These models are ideal for screening drug efficacy, studying immune responses, and evaluating anti-fibrotic therapies.

Genetic and Transgenic Models

Genetic and transgenic models involve the use of knockout or transgenic mice, such as Nfe2l2 knockout (B6.129P2-Nfe2l2/MymRbrc), Abcb4 knockout (FVB.129P2-Abcb4tm1Bor/J), and TGFBR2 transgenic strains. These models spontaneously develop features of PBC, including biliary injury, cholestasis, and fibrosis, due to targeted genetic alterations. Their major advantage lies in mimicking the genetic and immunological underpinnings of human PBC, allowing for mechanistic studies and long-term efficacy testing of disease-modifying treatments.

Surgically-Induced Models

Surgically-induced models, such as bile duct ligation (BDL) in C57BL/6 mice and Wistar rats, replicate cholestatic injury and subsequent fibrosis by physically obstructing bile flow. The BDL procedure is well-established and results in rapid, consistent development of biliary fibrosis, making it highly suitable for evaluating anti-fibrotic and hepatoprotective compounds. This model type is particularly valuable for preclinical pharmacology and toxicology studies.

Immune-Mediated Models

Immune-mediated models utilize the administration of biological agents, such as bovine serum albumin, MART-1/gp100/tyrosinase/GM-CSF, Freund’s adjuvant, and pertussis toxin, to elicit autoimmune responses against biliary epithelial cells. These models effectively recapitulate the immunopathological features of PBC, including portal inflammation and bile duct destruction. They are especially useful for studying disease mechanisms, immune modulation, and evaluating immunotherapies.

Protheragen offers a full-spectrum in vivo PBC model development service, encompassing model selection and validation, customized study design, compound administration, and comprehensive endpoint analysis. Key efficacy endpoints include serum biochemistry (ALT, AST, ALP, bilirubin), histopathological assessment (bile duct damage, fibrosis scoring), immunohistochemistry, cytokine profiling, and molecular analyses (qPCR, Western blotting). Our analytical capabilities extend to advanced imaging, flow cytometry, and omics-based approaches. Rigorous quality control measures—such as standardized protocols, genetic authentication of strains, and reproducibility assessments—ensure data integrity and scientific validity throughout the study lifecycle.

Partnering with Protheragen provides access to industry-leading expertise, state-of-the-art facilities, and a broad array of validated PBC animal models. Our collaborative approach accelerates the translation of scientific discoveries into therapeutic breakthroughs, ensuring high-quality, actionable data for your preclinical programs. Contact us today to discuss your research goals and discover how our PBC model development services can empower your next project.