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 #
7K08NS001467-05
Application #
3084552
Study Section
Neurological Disorders Program Project Review A Committee (NSPA)
Project Start
1990-08-01
Project End
1995-07-31
Budget Start
1993-09-30
Budget End
1994-07-31
Support Year
5
Fiscal Year
1993
Total Cost
Indirect Cost
Name
Yale University
Department
Type
Schools of Medicine
DUNS #
082359691
City
New Haven
State
CT
Country
United States
Zip Code
06520
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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