C12573: Transgenic HFR Mouse Model for Asthma and Allergy Drug Discovery
Novelty:
A mouse strain harboring lung epithelial cell-targeted inducible HRF, permitting the site-specific, regulatable HRF over-expression to study its use as a drug target for asthma and allergies.
Value Proposition:
Asthma is a prevalent chronic lung disorder characterized by inflammation and narrowing of the airways that can be efficiently controlled, yet, to date is incurable. Histamine releasing factor (HRF) has been suggested as a potential therapeutic target for asthma and other allergic reactions; however, detailed studies to explore its therapeutic application have been impeded by the lack of HRF animal models. Here, inventors created a transgenic mouse model enabling the inducible expression of tracer-HRF in lung epithelium, presenting the first in vivo experimental system to assess HRF function and its potential as a drug target for asthma and allergies. Advantages include:
- Inducible targeted HRF-overexpression enables detailed functional characterization in disease development
- Facilitates discovery of compounds targeting HRF for asthma and other allergic reactions
Technical Details:
Johns Hopkins researchers have generated a transgenic mouse strain conditionally expressing detectable HRF in lung epithelial cells, valuable as an in vivo model for the detailed functional characterization of HRF as a novel drug target for asthma and allergies. HRF has a wide range of intracellular and extracellular functions, including stimulating the release of histamine and other immuno-inflammatory molecules. Deletion of hrf in mice in embryonic lethal; hence, to study the proposed exploitation of HRF for asthma treatment, inventors engineered a transgenic mouse strain carrying tetracycline-inducible EGFP-tagged HRF under control of lung epithelium-specific promoter CC10. Importantly, upon challenge with ovalbumin (OVA), conditional targeted HRF over-expression in transgenic mice exacerbates the asthmatic response, leading to notably elevated levels of proinflammatory cytokines and immune cells in serum and bronchoalveolar lavage (BAL). Therefore, this technology presents an excellent in vivo system to elucidate HRF biology and its use for improved management of asthma and other allergic reactions.
Looking for Partners:
To develop & commercialize this technology as an in vivo model for asthma drug discovery.
Stage of Development:
Pre-Clinical
Data Availability:
Animal data
Publications/Associated Cases:
PLoS One. 2010 Jun 11;5(6):e11077.
