The axonal growth cone is critical to the development and maintenance of the uniquely complex and specific synaptic connections which underlie nervous system function. GAP-43 is a neuronal protein whose expression is closely correlated with growth cone activity in development and regeneration, and with synaptic plasticity. Homologous recombination will be employed to develop animals and cell lines incapable of expressing GAP-43. This technique relies on crossing over between an exogenous mutated DNA molecule and the endogenous gene to replace a normal allele with a mutated copy. In animals and cell lines with deletion of GAP-43, the importance of the protein for growth cone function will be analyzed. This information will allow creation of models and perhaps rational therapies for some disease states in which neural development, regeneration or plasticity are flawed. Examples include developmental disorders, neurite regeneration in neuropathy and perhaps in recovery from central injuries like stroke, and learning in memory disorders with impaired synaptic plasticity.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Clinical Investigator Award (CIA) (K08)
Project #
5K08NS001467-03
Application #
3084550
Study Section
Neurological Disorders Program Project Review A Committee (NSPA)
Project Start
1990-08-01
Project End
1995-07-31
Budget Start
1992-08-01
Budget End
1993-07-31
Support Year
3
Fiscal Year
1992
Total Cost
Indirect Cost
Name
Massachusetts General Hospital
Department
Type
DUNS #
City
Boston
State
MA
Country
United States
Zip Code
02199
Holland, Scott K; Vannest, Jennifer; Mecoli, Marc et al. (2007) Functional MRI of language lateralization during development in children. Int J Audiol 46:533-51
Xie, R; Li, L; Goshima, Y et al. (1995) An activated mutant of the alpha subunit of G(o) increases neurite outgrowth via protein kinase C. Brain Res Dev Brain Res 87:77-86
Strittmatter, S M; Igarashi, M; Fishman, M C (1994) GAP-43 amino terminal peptides modulate growth cone morphology and neurite outgrowth. J Neurosci 14:5503-13