TY - JOUR T1 - Targeted Overexpression of the Neurite Growth-Associated Protein B-50/GAP-43 in Cerebellar Purkinje Cells Induces Sprouting after Axotomy But Not Axon Regeneration into Growth-Permissive Transplants JF - The Journal of Neuroscience JO - J. Neurosci. SP - 8778 LP - 8791 DO - 10.1523/JNEUROSCI.17-22-08778.1997 VL - 17 IS - 22 AU - Annalisa Buffo AU - Anthony J. D. G. Holtmaat AU - Tiziana Savio AU - J. Sjef Verbeek AU - John Oberdick AU - A. Beate Oestreicher AU - Wilhelm Hendrik Gispen AU - Joost Verhaagen AU - Ferdinando Rossi AU - Piergiorgio Strata Y1 - 1997/11/15 UR - http://www.jneurosci.org/content/17/22/8778.abstract N2 - B-50/GAP-43 is a nervous tissue-specific protein, the expression of which is associated with axon growth and regeneration. Its overexpression in transgenic mice produces spontaneous axonal sprouting and enhances induced remodeling in several neuron populations (Aigner et al., 1995; Holtmaat et al., 1995). We examined the capacity of this protein to increase the regenerative potential of injured adult central axons, by inducing targeted B-50/GAP-43 overexpression in Purkinje cells, which normally show poor regenerative capabilities. Thus, transgenic mice were produced in which B-50/GAP-43 overexpression was driven by the Purkinje 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 growth phenomena, which never occurred in wild-type mice, the severed transgenic axons were not able to regenerate, either spontaneously or into embryonic neural or Schwann cell grafts placed into the lesion site. Finally, although only a moderate Purkinje cell loss occurred in wild-type cerebella after axotomy, a considerable number of injured transgenic neurons degenerated, but they could be partially rescued by the different transplants placed into the lesion site. Thus, B-50/GAP-43 overexpression substantially modifies Purkinje cell response to axotomy, by inducing growth processes and decreasing their resistance to injury. However, the presence of this protein is not sufficient to enable these neurons to accomplish a full program of axon regeneration. ER -