Transgenic Ferret Models Define Pulmonary Ionocyte Diversity and Function
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PROVIDER: PRJNA977233 | ENA |
REPOSITORIES: ENA
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Project description:Speciation leads to adaptive changes in organ cellular anatomy and physiology. These evolutionary changes create challenges for studying rare cell type functions that diverge between human and mice. Rare CFTR-rich pulmonary ionocytes exist throughout the cartilaginous airways of humans, but limited presence and divergent biology in the proximal trachea of mice has prevented the use of traditional transgenic models to elucidate ionocyte functions in the airway. Here we describe the creation and use of novel conditional genetic ferret models to dissect pulmonary ionocyte biology and function by enabling ionocyte lineage tracing (FOXI1-CreERT2::ROSA-TG), ionocyte ablation (FOXI1-KO), and ionocyte-specific deletion of CFTR (FOXI1-CreERT2::CFTRL/L). By comparing these models to cystic fibrosis (CF) ferrets, we demonstrate that ionocytes control airway surface liquid (ASL) absorption, secretion, pH, and mucus viscosity—leading to reduced ASL volume and impaired mucociliary clearance in CF, FOXI1-KO, and FOXI1-CreERT2::CFTRL/L ferrets. These processes were regulated by CFTR- dependent ionocyte transport of Cl– and HCO3–, as determined electrophysiologically and by single-cell imaging with a conditionally activated halide fluorescent sensor. Single-cell transcriptomics, using pulse-seq of lineage-traced ionocyte-enriched cultures, revealed three subtypes of pulmonary ionocytes with unique biologic functions and a common rare cell progenitor of ionocytes, tuft, and neuroendocrine cells. Thus, rare pulmonary ionocytes perform critical CFTR-dependent functions in the proximal airway that are hallmark features of CF airway disease. These studies provide a road map for using conditional genetics in the first non- rodent mammal to address gene function, cell biology, and disease processes that have greater evolutionary conservation between humans and ferrets.
2023-08-01 | GSE233654 | GEO
Project description:The domestic ferret (Mustela putorius furo) has been used as animal model for decades, largely because its susceptibility to infection with a large number of pathogens such as influenza virus, SARS Corona virus and Canine distemper virus. Despite its importance for biomedical research, little is known about the genome of the M. Furo. The number of reagents for molecular and immunological analysis is thus restricted. To circumvent this, we present here a parallel sequencing effort to produce an extensive EST dataset derived from a normalized ferret cDNA library made from mRNA from ferret blood, liver, lung, spleen and brain. We produced more than 500000 sequence reads that were assembled into over 15000 partial ferret transcripts. These ESTs were combined with the available ferret sequences in the GenBank to develop a ferret specific microarray platform. Using this array, we detected tissue specific expression patterns which were confirmed by quantitative real time PCR assays and comparison to orthologous transcription profiles of mouse and human. We also present a set of 41 ferret transcript with even transcription profile across the tested tissues, indicating their usefulness as housekeeping genes. This study paves way for development of additional reagents for analysis of the ferret model. Three biological replicates of blood, lung, spleen, liver and brain was hybridized to the ferret specific microarray.
2010-09-13 | E-GEOD-19398 | biostudies-arrayexpress
Project description:Characterization of Ferret Microbiota
| PRJEB53675 | ENA
Project description:The domestic ferret (Mustela putorius furo) has been used as animal model for decades, largely because its susceptibility to infection with a large number of pathogens such as influenza virus, SARS Corona virus and Canine distemper virus. Despite its importance for biomedical research, little is known about the genome of the M. Furo. The number of reagents for molecular and immunological analysis is thus restricted. To circumvent this, we present here a parallel sequencing effort to produce an extensive EST dataset derived from a normalized ferret cDNA library made from mRNA from ferret blood, liver, lung, spleen and brain. We produced more than 500000 sequence reads that were assembled into over 15000 partial ferret transcripts. These ESTs were combined with the available ferret sequences in the GenBank to develop a ferret specific microarray platform. Using this array, we detected tissue specific expression patterns which were confirmed by quantitative real time PCR assays and comparison to orthologous transcription profiles of mouse and human. We also present a set of 41 ferret transcript with even transcription profile across the tested tissues, indicating their usefulness as housekeeping genes. This study paves way for development of additional reagents for analysis of the ferret model.
2010-09-13 | GSE19398 | GEO
Project description:Domestic ferret with Bionano hybrid scaffolds
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Project description:To identify differently expressed genes between ferret and mouse astrocytes, we performed RNA-seq studies on primary ferret and mouse astrocytes cultured in serum free medium. We isolated primary astrocytes from mixed glial cultures which are prepared from the cortices of ferrets and mice at postnatal day 1. Each biological replicate was generated from 2 individuals of the same species. We detected substantial changes in the expression of genes associated with cell proliferation and migration, and identified ferret astrocyte-specific genes.
2022-09-20 | GSE201199 | GEO
Project description:Black-footed Ferret Genome Analysis
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Project description:The objective of this study was test and compared two custom designed ferret Agilent microarrays
2014-07-18 | GSE49060 | GEO
Project description:Chronic obstructive pulmonary disease (COPD) is a heterogeneous disease typified by not fully reversible and often progressive airflow obstruction, along with persistent respiratory symptoms. This gap is due to lack of animal models that more closely mimic human COPD are needed to bridge translational gaps. Commonly used mice model produces primarily emphysematous disease and do not develop features pathognomonic for chronic bronchitis. Suggesting the potential for additional molecular insights to be obtained from animal models that exhibit COPD with features of chronic bronchitis and emphysema, as in humans. We sought to identify whether our ferret model of COPD captures unique genetic signatures in comparison to mouse models that can help improve understanding of the molecular pathogenesis of COPD and promote the development of new and effective therapies.
2022-10-19 | GSE193749 | GEO