TARGETED OVEREXPRESSION OF THE NEURITE GROWTH-ASSOCIATED PROTEIN B-50GAP-43 IN CEREBELLAR PURKINJE-CELLS INDUCES SPROUTING AFTER AXOTOMY BUT NOT AXON REGENERATION INTO GROWTH-PERMISSIVE TRANSPLANTS/

B-50/GAP-43 is a nervous tissue-specific protein, the expression of wh ich is associated with axon growth and regeneration. Its overexpressio n in transgenic mice produces spontaneous axonal sprouting and enhance s induced remodeling in several neuron populations (Aigner et al., 199 5; Holtmaat et al., 1995). We examined the capacity of this protein to increase the regenerative potential of injured adult central axons, b y inducing targeted B-50/GAP-43 overexpression in Purkinje cells, whic h normally show poor regenerative capabilities. Thus, transgenic mice were produced in which B-50/GAP-43 overexpression was driven by the Pu rkinje cell-specific L7 promoter. Uninjured transgenic Purkinje cells displayed normal morphology, indicating that transgene expression does not modify the normal phenotype of these neurons. By contrast, after axotomy numerous transgenic Purkinje cells exhibited profuse sprouting along the axon and at its severed end. Nevertheless, despite these gr owth phenomena, which never occurred in wild-type mice, the severed tr ansgenic axons were not able to regenerate, either spontaneously or in to embryonic neural or Schwann cell grafts placed into the lesion site . Finally, although only a moderate Purkinje cell loss occurred in wil d-type cerebella after axotomy, a considerable number of injured trans genic neurons degenerated, but they could be partially rescued by the differ; ent transplants placed into the lesion site. Thus, B-50/GAP-43 overexpression substantially modifies Purkinje cell response to axoto my, by inducing growth processes and decreasing their resistance to in jury. However, the presence of this protein is not sufficient to enabl e these neurons to accomplish a full program of axon regeneration.