Alternatively spliced isoforms of FE65 serve as neuron-specific and non-neuronal markers

FE65 is predominantly expressed in brain and is especially rich in the regi ons with the highest densities of neurons. The FE65 protein binds to an int racellular domain of the beta-amyloid precursor protein (beta PP) and may m odulate the production of beta-amyloid peptide (AP), One of FE65 exons, a m ini-exon (exon 9, 6 bp), is alternatively spliced, giving rise to two isofo rms varying only in 6 base pairs. We quantitated the two isoforms by a sens itive reverse transcription-competitive polymerase chain reaction technique , and characterized their expressions in various tissues and cell cultures, and the kinetics of expression of the two isoforms in P19 embryonal carcin oma cell lines during neuronal differentiation Our results show that the ex on 9-inclusive (E9) form, the more abundant form in brain, was exclusively expressed in neurons, while the exon 9-exclusive (Delta E9) form was widely expressed in all non-neuronal cells, but was not expressed in differentiat ed neurons. When P19 cells were differentiated to neurons, expression of FE 65 was significantly up regulated (similar to 30-fold) and the splicing pat tern of the FE65 pre-mRNA was switched from the Delta E9 pattern to the E9 form. Based upon their distinctive expression patterns, these two isoforms may serve as neuronal and non-neuronal markers, and determination of their ratios may have applications in neuropathological diagnosis. (C) 1999 Wiley -Liss,Inc.