Gene targeting in embryonic stem (ES) cells is being used to inactivate (knock-out) genes and use the mutated ES cells to generate mice with a mutation at the targeted locus. The cystatin C gene has been cloned and used to make gene targeting constructs. Cystatin-C knock-out mice have been made. These mice do not produce any mouse Cystatin C RNA or protein. They breed normally, but are less aggressive than normal mice and have reduced horizontal movement activity. Further pathological and neurological evaluation is in progress. Human mutant Cystatin C knock-in mice are also being developed in order to make an animal model for hereditary stroke. The knock-in is done with a mutant Cystatin C gene from a patient with hereditary cerebral angiopathy.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Intramural Research (Z01)
Project #
1Z01NS002878-04
Application #
2579641
Study Section
Special Emphasis Panel (DMN)
Project Start
Project End
Budget Start
Budget End
Support Year
4
Fiscal Year
1996
Total Cost
Indirect Cost
City
State
Country
United States
Zip Code