DEVELOPMENTAL EXPRESSION OF THE GENE ENCODING GROWTH-ASSOCIATED PROTEIN-43 (GAP43) IN THE BRAINS OF NORMAL AND ANEUPLOID MICE

The gene encoding growth-associated protein 43 (Gap43), a neuronal phosphoprotein associated with axonal outgrowth and synaptic plasticity, is located on mouse chromosome 16 (MMU16). We examined the developmental expression of Gap43 in normal, trisomy 16 (Ts16), and trisomy 19 (Ts19) mouse brain using northern blot analysis and in situ hybridization as a first step toward understanding the neurobiologic consequences of increased gene dosage on brain development. Gap43 expression was detected by in situ hybridization throughout the mesencephalon, rhombencephalon, spinal cord, and first branchial arch in whole embryos as early as day 10 of gestation (E10). By E15, Gap43 expression was localized to cells in the retina, the olfactory bulbs, and anterior olfactory structures, the cortical plate, the basal telencephalon, diencephalon, midbrain, hindbrain, and spinal cord. Northern blot analysis detected a threefold increase in Gap43 mRNA levels in the brains of normal mice between E12-E18. At E15, Gap43 mRNA levels were increased 35-40% in Ts16 mouse brain and decreased 10% in Ts19 mouse brain, relative to euploid littermate controls. Using in situ hybridization we found that overexpression of Gap43 occurred in the diencephalon, medial and lateral basal telencephalon, and cortical plate region in Ts16 mice relative to littermate controls. Thus, the degree of overexpression of Gap43 mRNA in Ts16 mice is consistent with that expected from gene dosage effects.