Columbia University

Technology Ventures

Mouse for human mitochondrial respiratory chain disease

Technology #2651

“Lead Inventor: Eric A. Schon Ph.D.

Mitochondrial respiratory chain disease studies using mouse model : Mitochondrial respiratory chain disease is a heterogeneous disorder, and several genes including Sco2 have been identified to result in this disease. Sco2 gene mutations cause fatal, early-onset cytochrome c oxidase (COX) deficiency that affects skeletal muscles, heart, kidney, liver, brain and connective tissues. In addition, these gene mutations can result in heart muscle weakening and brain dysfunction. Currently there is no treatment for this disorder, but there are novel drugs under development. A good animal model may serve to evaluate these agents before they embark on clinical trials. Also, a good animal model is a useful tool to better understand the pathological origin of the disease and further develop new therapeutic approaches.

In vivo mouse model for drug development in respiratory disease : This invention described an in vivo animal model of Sco2 deficiency, which is the first in vivo model that recapitulates the feature of this Sco2 gene-associated human disorder. This invention provides transgenic mice harboring a Sco2 knockout (KO) allele and a mutated Sco2 knock-in allele, corresponding to a common mutation found in human Sco2-mutated patients. This transgenic mouse displays reduction in COX activity in examined tissues, including brain, heart, liver, and skeletal muscle. This transgenic mouse exhibits deficit in muscle strength. This transgenic mouse mimics the expected phenotype indicating it represents a good model for human disease.

Applications: • Develop therapeutic approaches to treat human respiratory chain disease. • Develop therapeutic targets for aging associated disease including Alzheimer’s Disease, Parkinson’s Disease and dystonia. • Screen drugs and evaluating the efficacy of treatments for those diseases.

Advantages: • This invention offered an in vivo mouse model that captures the disease state and has greater relevance to the disorder. • This animal line has normal life span, in contrast to the lethal phenotype observed in the homozygous Sco2 KO mice. • Mice, compared with other animal models, are relatively economical to maintain, which reduces the developmental costs.

Patent Status: Copyright / Animals available for fee

Licensing Status: Available for Licensing and Sponsored Research Support

Publications: Yang H, Brosel S, Schon EA et al. Analysis of mouse models of cytochrome c oxidase deficiency owing to mutations in Sco2. Hum Mol Genet. 2009 Oct 16