Systems Genetics of Tuberous Sclerosis Complex Outcomes Using BXD Recombinant Inbred Mice
Abstract
The goal of this hypothesis development project is to demonstrate that diversity in genetic background significantly influences tuberous sclerosis complex (TSC) outcomes in mice. This will show that it is possible to genetically map susceptibility and resilience genes to different classes of TSC outcomes, including TSC-associated neurological disorders, epilepsy, and brain malformations. During this funding period we learned that the available Tsc1-mutant mouse model has a mixed genetic background, meaning that its genome is a combination of multiple inbred strain genomes. This introduces unwanted genetic variability into the breeding scheme for our experiments. To overcome this, we have undertaken a backcross breeding program to purify the genetic background of the Tsc1-mutant mouse to eliminate this variability in future experiments. The significant development to date is that we have finished breeding the second generation of this backcross, resulting in a mouse with an approximately 75 pure genome. We will use these mice to make Tsc1 knockouts and go forward with those knockouts to study the effects of genetic background on TSC outcomes. We will complete the backcross breeding scheme to create a mouse with around 95 purity in parallel with other experiments.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jul 01, 2020
- Accession Number
- AD1108712
Entities
People
- John M. Mahoney
Organizations
- University of Vermont