TSC2 Happloinsufficiency Leads to a Mutator Phenotype
Abstract
Tuberous Sclerosis Complex (TSC) patients develop tumors of the brain, kidney, skin and heart upon loss of either the TSC1 or TSC2 gene, and we are interested in elucidating early molecular events that contribute to loss of TSC2 and in understanding how TSC2 heterozygosity might contribute to this process. Our lab uses the Eker rat, which possesses an inactivating retroviral insertion in one Tsc2 allele (Tsc2Ek/+), as a model to better understand how Tsc2 heterozygosity contributes to cancer susceptibility. The goal of this award was to determine whether Tsc2 haploinsufficiency generated a mutator phenotype in target tissues in vivo that possibly contributed to early events in tumorigenesis within TSC2+/-individuals and establish an in vitro model of Tsc2 haploinsufficiency. We were able to successfully establish an in vitro method of depleting Tsc2 expression, and we are performing experiments to analyze mutation frequency and spectra in vitro in the presence or absence of Tsc2 expression. In addition, our preliminary results indicate that rats heterozygous for Tsc2 have a higher mutation frequency in vivo as they age compared to wild-type rats.
Document Details
- Document Type
- Technical Report
- Publication Date
- Nov 01, 2006
- Accession Number
- ADA470640
Entities
People
- John D. Short
Organizations
- The University of Texas MD Anderson Cancer Center