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A novel rabbit model offers promising insights into the pancreatic complications associated with cystic fibrosis, potentially reshaping diabetes management in CF patients.
This research is crucial as it opens avenues for better understanding and treatment of cystic fibrosis-related diabetes (CFRD), impacting long-term health outcomes for CF patients.
A team of researchers from the First Hospital of Jilin University, led by Dr. Jie Xu, has developed a rabbit model to study cystic fibrosis-related pancreatic endocrine pathology. Using CRISPR/Cas9 technology, young rabbits mimic human pancreatic changes seen in CF, such as fibrosis and reduced insulin production, providing insights into CF-related diabetes. This model could lead to new therapeutic strategies for managing CFRD. The research underscores the model's potential to replace expensive models like pigs and ferrets in terms of cost-effectiveness and accessibility.
The new rabbit model effectively replicates human-like CF pancreatic pathology. Using CRISPR/Cas9, the researchers created a CF rabbit model showing typical pancreatic abnormalities.
This model aids in understanding CFRD's pathophysiology, crucial for therapeutic development. The model causally links CFTR mutations with endocrine pathology.
Researchers developed the rabbit model by employing CRISPR/Cas9 gene-editing to induce CFTR mutations. This ensures that the rabbits mirror the human condition of cystic fibrosis, particularly focusing on pancreatic lesions. These rabbits displayed typical CF pancreatic changes such as fibrosis, vacuolar degeneration, and reduced insulin production.
"Our findings suggest that rabbits with CF replicate key aspects of CF pancreatic disease, positioning them as a valuable model for translational research," said Dr. Jie Xu, the corresponding author.
This model overcomes the limitations of previous large-animal models like pigs, which, while effective, are costly and require specialized care. Rabbits, in contrast, are more affordable and easily handled in laboratory settings.
Pancreatic lesions in CF rabbits provide insights into CFRD's progression. The study identified a precursor stage of CFRD in young rabbits, mirroring human disease progression.
Understanding early stages allows for timely intervention in disease progression. The similarities between rabbit and human CF pathologies allow the rabbit model to inform about human disease.
The study uncovered that CF rabbits develop an indeterminate glucose tolerance stage, characterized by delayed glucose clearance and reduced insulin production. This stage is analogous to early CFRD manifestations in humans and provides a critical window for therapeutic intervention.
Interestingly, the research also found sex-based differences, with female rabbits more prone to the indeterminate stage, reflecting similar trends in human CFRD demographics.
The rabbit model could revolutionize CF research and treatment strategies. The model offers a cost-effective and reliable means for CF research, paving the way for novel treatments.
Addressing pancreatic dysfunction is essential for improving life expectancy and quality of life in CF patients. By examining the model's findings, researchers can deduce potential therapeutic strategies for human application.
Researchers emphasize that this model represents an opportunity for extensive research into CF-related pancreatic issues. It is not only cost-effective but expands the research potential to a broader range of laboratories that might lack access to more specialized animal models.
With CFTR modulators like Trikafta improving patient longevity, addressing metabolic and endocrine complications becomes increasingly crucial. Early intervention strategies developed using the rabbit model could delay or prevent CFRD onset, significantly impacting patient care.
Liang X, Hou X, Zhang K, Xu J. Endocrine pathology in young rabbits with cystic fibrosis. BMJ Gastroenterology. 2024;2(4):e100102. doi:10.1136/egastro-2024-100102.
First Hospital of Jilin University. New rabbit model provides insights into CF-related pancreatic endocrine pathology. News Medical. 2025. Accessed January 20, 2025. https://www.news-medical.net/news/20250117/New-rabbit-model-provides-insights-into-CF-related-pancreatic-endocrine-pathology.aspx