Modeling Phenotypes of Tuberous Scerosis in the Mouse
Final rept. 10 Jan 2005-9 Jan 2008
WASHINGTON UNIV ST LOUIS MO
Pagination or Media Count:
The overall goal of this project was to generate a mouse model of the smooth muscle-related facets of tuberous sclerosis, specifically in an attempt to model the lung phenotype seen in a subset of TS patients and patients with LAM. We have conditionally targeted the TSC1 gene in smooth muscle, which results in mortality at approximately 10 weeks of age. This mouse provided a useful model in which to investigate the function of individual MMPs or other proteins in this pathological progression, and to evaluate relevant therapeutic interventions such as rapamycin. We found that MMP-9 was induced in the lungs of these mice. However, upon breeding the MMP-9 knockout allele into this model, the absence of MMP- 9 did not change the phenotype, ie., the mice still died at 10 weeks of age. Similarly, administration of rapamycin 75 microgramsmouse, 3X week beginning at week 4 did not alter the lifespan of the mice.
- Anatomy and Physiology