Four structurally distinct neuron-specific olfactomedin-related glycoproteins produced by differential promoter utilization and alternative mRNA splicing from a single gene.

Four structurally related neuron-specific 1B426b mRNAs, designated AMY, BMY, AMZ, and BMZ, have been isolated from rat brain cDNA libraries. The four mRNAs are related to one another by their shared M region and by two pairs of alternative 5' (A, B) or 3' (Y, Z) regions. All four possible combinations were detected. The four transcripts are derived by differential promoter utilization (to generate A or B 5' ends) and alternative splicing (to generate Y or Z 3' ends) of the primary transcripts of the single D2Sutle gene. All four mRNAs were detected in most brain regions, but were enriched within the cortex and hippocampus. In the pituitary only the two A-type and in the adrenal glands only the two B-type mRNAs were detected. In situ hybridization shows a highly heterogeneous distribution across brain regions, paralleling the Northern blot results and additionally identifying the reactive cells as neurons. The cDNAs encode related glycoproteins of 125, 153, 457, and 485 amino acids, which have been detected immunochemically. The AMZ and BMZ proteins show significant sequence similarity with olfactomedin, an extracellular matrix protein of bullfrog olfactory epithelium, suggesting the possibility of a matrix-related function for these rat glycoproteins in neurons and neurosecretory cells.