Expression of the adenomatous polyposis coli (APC) gene derived exon BS (e.g., brain-specific exon) has been analyzed by RT-PCR. Four novel APC mRNA isoforms derived from alternative splicing of exons IA, BS and I were identified, which were ubiquitously expressed. One novel cDNA was characterized by cloning and DNA sequence analysis, which combined the exon IA (identical with exon 0.3) 3' end with nucleotide position + 101 of intron IA and continued throughout exon BS. A second cDNA isoform was isolated, which joined the 3' end of exon IA with nucleotide position + 118 of exon BS. Both novel isoforms were found to be expressed together with a third novel APC exon connection, which was specified by exon BS/2 joining. This interesting exon junction resulted in novel deduced amino terminal open reading frames, which are completely in-frame with sequences located further downstream. Systematic exon connection analyses revealed that APC transcripts with exon BS/2 junctions were predominantly detected with a fixed exon composition. RT-PCR analyses did not identify facultative skipping of exons 9, 10A and 14 in this type of mRNA, in contrast to exon I-containing APC transcripts analyzed from the same cDNA pool under identical conditions. Hence, exon I skipping of exon BS-positive mRNA molecules might preferentially encode unique APC polypeptide chains, which are characterized by an alternative amino terminus and extended heptad repeat structures due to combined incorporation of exons 9 and 10A.
