SYMPATHETIC AND SENSORY AXONS INVADE THE BRAINS OF NERVE GROWTH-FACTOR TRANSGENIC MICE IN THE ABSENCE OF P75(NTR) EXPRESSION

Collateral sprouting, a nerve growth factor (NGF)mediated growth respo nse of undamaged peripheral axons, can be divided into reparative and aberrant axonal growth. We have previously shown that aberrant growth occurs in transgenic mice overexpressing NGF centrally under the contr ol of the glial fibrillary acidic protein promoter. Both sympathetic a nd sensory fibers, stained immunohistochemically for tyrosine hydroxyl ase and calcitonin gene-related peptide, respectively, invade the cere bellum of postnatal transgenic mice, whereas no such axons are seen in age-matched wild-type cerebellum. Recent examination of mice possessi ng a null mutation for p75(NTR) has suggested that axon growth may be influenced by the functional expression of this receptor. To address t he potential role of p75(NTR) in axon growth, we have generated a new line of hybrid mice overexpressing NGF but lacking functional p75(NTR) expression. Postnatal (day 14) hybrid cerebellum possessed fewer aber rant sensory and sympathetic fibers compared to their age-matched tran sgenic counterparts. By adulthood, however, hybrid cerebellum displaye d a robust plexus of axons stained immunohistochemically for calcitoni n gene-related peptide and tyrosine hydroxylase. No neuronal or nonneu ronal localization of p75(NTR)-immunoreactive elements was observed in postnatal and adult hybrid cerebellum. Interestingly, sympathetic axo ns within the hybrid cerebellum displayed a markedly reduced axon dens ity and staining intensity for NGF, suggesting a possible alteration i n axonal sequestration of-NGF. These results show that p75(NTR) is not vital for new growth of NGF-sensitive sympathetic and sensory axons a nd that immunohistochemical detection of NGF at sympathetic axons requ ires the functional expression of p75(NTR). (C) 1998 Academic Press.