ArticleJCI insight2022
Ferret models of alpha-1 antitrypsin deficiency develop lung and liver disease.
Article in JCI insight, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 26 citations in OpenAlex.
- Polymerized Z-α-1 antitrypsin leads to lung injury in a murine model of emphysema.JCI insight · 2026Article
- Dual SORT LNPs for multi-organ base editing.Nature biotechnology · 2026Article
- Multi-modal screening for synergistic neuroprotection of mild extremely preterm brain injury.Bioengineering & translational medicine · 2026Article
- Ferrets and genetically modified ferrets as model organisms in biomedical research: a review.Frontiers in genome editing · 2026Review
- A ferret model demonstrates sustained fibrosis, restrictive physiology, and airway proximalization.NPJ Regenerative medicine · 2025Article
- Ferret model of bleomycin-induced lung injury shares features of human idiopathic pulmonary fibrosis.NPJ Regenerative medicine · 2025Article
- A single amino acid variant in the variable region I of AAV capsid confers liver detargeting.PLoS pathogens · 2025Article
- Novel Cystic Fibrosis Ferret Model Enables Visualization of CFTR Expression Cells and Genetic CFTR Reactivation.Human gene therapy · 2025Article
- Can Proteomics Play a Significant Role in the Identification of Biomarkers for Alpha1-Antitrypsin Deficiency?International journal of molecular sciences · 2025Review
- Ferret model of bleomycin-induced lung injury shares features of human idiopathic pulmonary fibrosis.bioRxiv : the preprint server for biology · 2025Article
- Targeted animal models for preclinical assessment of cellular and gene therapies in pancreatic and liver diseases: regulatory and practical insights.Cytotherapy · 2025Review
- Spatial covariance reveals isothiocyanate natural products adjust redox stress to restore function in alpha-1-antitrypsin deficiency.Cell reports. Medicine · 2025Article
- Durable transgene expression and efficient re-administration after rAAV2.5T-mediated fCFTRΔR gene delivery to adult ferret lungs.Molecular therapy. Methods & clinical development · 2024Article
- In utero and postnatal ivacaftor/lumacaftor therapy rescues multiorgan disease in CFTR-F508del ferrets.JCI insight · 2024Article
- Genome Editing in Ferret Airway Epithelia Mediated by CRISPR/Nucleases Delivered with Amphiphilic Shuttle Peptides.Human gene therapy · 2023Article
- Immunohistochemical detection of MUC5AC and MUC5B mucins in ferrets.BMC research notes · 2023Article
- Immunosuppression reduces rAAV2.5T neutralizing antibodies that limit efficacy following repeat dosing to ferret lungs.Molecular therapy. Methods & clinical development · 2023Article
- Capturing the conversion of the pathogenic alpha-1-antitrypsin fold by ATF6 enhanced proteostasis.Cell chemical biology · 2023Article
- Liver gene therapy: The magic bullet for the sick lung.Molecular therapy. Methods & clinical development · 2022Article
- Novel Gene-Correction-Based Therapeutic Modalities for Monogenic Liver Disorders.Bioengineering (Basel, Switzerland) · 2022Review
Corrections and comments
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Authors and funding
24 authors at 3 institutions in 2 countries.
Funding
Abstract
Alpha-1 antitrypsin deficiency (AATD) is the most common genetic cause and risk factor for chronic obstructive pulmonary disease, but the field lacks a large-animal model that allows for longitudinal assessment of pulmonary function. We hypothesized that ferrets would model human AATD-related lung and hepatic disease. AAT-knockout (AAT-KO) and PiZZ (E342K, the most common mutation in humans) ferrets were generated and compared with matched controls using custom-designed flexiVent modules to perform pulmonary function tests, quantitative computed tomography (QCT), bronchoalveolar lavage (BAL) proteomics, and alveolar morphometry. Complete loss of AAT (AAT-KO) led to increased pulmonary compliance and expiratory airflow limitation, consistent with obstructive lung disease. QCT and morphometry confirmed emphysema and airspace enlargement, respectively. Pathway analysis of BAL proteomics data revealed inflammatory lung disease and impaired cellular migration. The PiZ mutation resulted in altered AAT protein folding in the liver, hepatic injury, and reduced plasma concentrations of AAT, and PiZZ ferrets developed obstructive lung disease. In summary, AAT-KO and PiZZ ferrets model the progressive obstructive pulmonary disease seen in AAT-deficient patients and may serve as a platform for preclinical testing of therapeutics including gene therapy.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.