The RCAS/RCAN retroviral vectors are in wide use as tools for studying development and oncogenesis in the avian system. The creation of transgenic mice that express a specific receptor for these vectors has significantly increased the flexibility of this system. We have developed lines of transgenic mice that express the receptor under the control of a tissue-specific promoter; this makes it possible to direct the vector to particular cells or tissues. This system can be used for lineage analysis; it will simplify studies of the effects of oncogenes and morphogenesis in vivo; in addition, the ability to make defined mutations in the mouse means that this can be an efficient model system to evaluate gene therapy strategies. We are particularly interested in the applications of this system to study the effects of aging skeletal muscle; however, we would point out that it should be relatively simple to use the RCAS/RCAN vectors and appropriate strains of subgroup A receptor mice both to study and test therapeutic strategies in a variety of other tissues.

Agency
National Institute of Health (NIH)
Institute
National Institute on Aging (NIA)
Type
Research Program Projects (P01)
Project #
5P01AG013329-03S1
Application #
2778402
Study Section
Project Start
Project End
Budget Start
1997-10-01
Budget End
1998-09-30
Support Year
3
Fiscal Year
1998
Total Cost
Indirect Cost
Name
Massachusetts General Hospital
Department
Type
DUNS #
City
Boston
State
MA
Country
United States
Zip Code
02199
Gonzalez, M; Ruggiero, F P; Chang, Q et al. (1999) Disruption of Trkb-mediated signaling induces disassembly of postsynaptic receptor clusters at neuromuscular junctions. Neuron 24:567-83
O'Malley, J P; Waran, M T; Balice-Gordon, R J (1999) In vivo observations of terminal Schwann cells at normal, denervated, and reinnervated mouse neuromuscular junctions. J Neurobiol 38:270-86
Barton-Davis, E R; Shoturma, D I; Musaro, A et al. (1998) Viral mediated expression of insulin-like growth factor I blocks the aging-related loss of skeletal muscle function. Proc Natl Acad Sci U S A 95:15603-7
Balice-Gordon, R J (1997) Age-related changes in neuromuscular innervation. Muscle Nerve Suppl 5:S83-7
Reddy, S; Smith, D B; Rich, M M et al. (1996) Mice lacking the myotonic dystrophy protein kinase develop a late onset progressive myopathy. Nat Genet 13:325-35