Our researchers have created a gene knockout mouse model that lacks the cytochrome c oxidase subunit IV-2 in order to study the gene’s effects on controlling asthma.
Background & Unmeet Need:
Asthma is an inflammatory disease of the airways that affects 155 million people of all ages worldwide. Cytochome c oxidase (CcO) is a multi-subunit enzyme located in the mitochondria and catalyzes electron transfer from cytochrome c to oxygen. It is the key enzyme of aerobic energy production and burns oxygen to eventually make energy, which in turn drives all cellular processes. These processes include airway constriction in the lung during asthma. The CcO subunit IV-2 gene (CcO4-2) is active in lung tissue and placenta. The presence of the CcO4-2 gene speeds up CcO activity, whereas its absence decreases its activity. Consequently, absence of the gene results in decreased energy, and researchers have discovered that knockout mice lacking this specific gene show reduced airway responsiveness.
Technology Description:
Our researchers have generated a knockout mouse model lacking the CcO4-2 gene. Along with the wild-type mice, they can be used to functionally study asthma. The CcO4-2 gene may also be a marker for asthma susceptibility, and thus mutations in the gene could be protective against asthma. Eventually, the CcO4-2 protein can be exploited as a new drug target for the treatment of asthma.
Commercial Applications:
- Research tool to functionally study asthma
- CcO4-2 gene can be used as a marker for asthma susceptibility
- CcO4-2 protein can be used as a drug target for asthma therapeutics
Stage of Development:
Animal models are available for distribution.
Competitive Advantages:
One of the few mechanistic models to study asthma (most are inflammatory models) and provides the following benefits:
- genetic vs. challenge model
- demonstrated constriction phenotype
- detailed, objective characterization of impact of gene deletion
- opportunity as research tool for lung and other tissue pathologies
Intellectual Property Status:
Patent application filed
Related publications or citations of work:
Huttemann, M. (2000) New isoforms of cytochrome c oxidase subunit IV in tuna fish. Biochim Biophys Acta, 1492: 25-258
Huttemann, M., Kadenbach, B., Grossman, LI. (2001) Mammalian subunit IV isoforms of cytochrome c oxidase. Gene, 267: 111-123
Huttemann, M., Lee, I., Liu, J., Grossman, L.I. (2007) Transcription of cytochrome c oxidase subunit IV-2 is controlled by a novel oxygen responsive element conserved in mammals, FEBS Journal, 274: 5737-48