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Characterization of a novel mouse model for alveolar epithelial type 2 cell regeneration
Author(s) -
Driscoll Barbara,
Lee Jooeun,
Reddy Raghava
Publication year - 2010
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.24.1_supplement.798.5
Subject(s) - regeneration (biology) , ganciclovir , thymidine kinase , biology , herpes simplex virus , microbiology and biotechnology , transgene , population , bystander effect , blot , cell , genetically modified mouse , surfactant protein c , gene , immunology , virus , medicine , genetics , human cytomegalovirus , environmental health
A lentiviral vector in which surfactant protein‐C (SP‐C) promoter drives a mutated Herpes Simplex Virus thymidine kinase gene (TKsr39) with enhanced affinity for ganciclovir (GCV) was used to create “SPCTK” transgenic mice on a Rosa R26R background. Descendants from one founder were analyzed for the impact of targeted alveolar epithelial type 2 cell (AEC2) depletion. R26R‐SPCTK mice dosed with 10mg/kg GCV over 7 days become lethargic and exhibit labored breathing. Quantitative immunohistological analysis of lung tissue shows a significant decrease in AEC2 and some decrease in bronchioalveolar stem cells (BASC) by day 7. No notable disruption of Clara cell and AEC1 populations due to bystander effects was observed but a moderate cellular infiltrate appeared in the latter stages of treatment. Compared to GCV‐treated R26R AEC2, GCV‐treated R26R‐SPCTK+/− AEC2 show negligible levels of pro‐SP‐C and minimal mature SP‐C protein present by Western blotting after 7 days GCV treatment. When R26R‐SPCTK mice are treated with 50mg/kg GCV for 2 days, more than 95% of AEC2 are eliminated by day 3 following treatment. By day 5, the number of AEC2 and level of SP‐C expression begins to increase in surviving animals, indicating the de novo appearance of an AEC2 population. Characterization of this regeneration is ongoing.