Generation of Alpha-1 Antitrypsin Knockout and PI*ZZ Ferrets Using Crispr/Cas9. A Genetic Model of Emphysema

Abstract

by engineering a conditional activator [b-catenin lacking degradation sites; Catnb loxP(ex3) ], targeted to lung MPCs using ABCG2CreERT2 with reporters: Rosa26 m-tdTomato/mGFPlox-stop . This lineage-labeling mouse model, in the presence or absence of Wnt activation, was subjected to vascular injury using SUGEN 5416 and hypoxia. Physiological endpoints of vascular injury; morphometrics, including stereology to measure mean linear intercept (MLI); and lineage analysis were performed. Murine and human MPCs, normal and COPD, were isolated by flow cytometry and analyzed in vitro in coculture analysis with MVECs to define physiological relevance of the cell-cell interactions.Rationale: The most prevalent genetic cause of chronic obstructive pulmonary disease is alpha-1 antitrypsin (A1AT) deficiency, a disorder that has yet to be widely modeled in animals because of species-specific differences between rodents and humans.