Regulated splicing of the amyloid precursor protein gene during postnatal development of the rat basal forebrain.

The expression of the amyloid precursor protein (APP) gene has been examined in the basal forebrain of rats from birth to adulthood. Levels of total APP mRNA are highest at birth and at postnatal day 15 (P15). The most abundant transcript in rat brain is APP-695, whose expression has previously been found to be largely restricted to the central nervous system. Comparison of the developmental profiles of APP-695 mRNA with that of Kunitz-protease inhibitor (KPI)-containing APP mRNA shows that the greatest difference in expression occurs at P15, when APP-695 message levels are over 6-fold higher than KPI-containing APP mRNA (APP-751, APP-770). This is the largest difference in the APP-695/KPI-APP ratio observed during postnatal development and coincides with the period of maximal neurotrophic responsiveness in the basal forebrain. These results suggest that the APP gene is alternatively spliced during postnatal development and that regulated expression of APP-695 may be influenced by neurotrophic factors in vivo.