TISSUE-DEPENDENT ALTERNATIVE SPLICING OF MESSENGER-RNA FOR NACP, THE PRECURSOR OF NON-A-BETA COMPONENT OF ALZHEIMERS-DISEASE AMYLOID

A cDNA clone encoding an alternatively spliced form of the precursor of the non-A beta component of Alzheimer's disease amyloid (NACP) was isolated from a human fetal brain cDNA library. This cDNA contains the entire NAC coding sequence but lacks an 84-base-pair nucleotide stretch 3' to the NAC sequence, resulting in a 112-amino-acid protein, NACP112, in contrast with the originally cloned molecule, NACP140. RT-PCR analysis demonstrated that the mRNA for two types of NACP mRNA are expressed in both fetal and adult brain. Northern blot analysis revealed that NACP140 mRNA was expressed mostly in brain and in minor amount in all the tissues examined. However, the expression levels of NACP 140 mRNA apart from brain were higher in heart, skeletal muscle, and pancreas, contrasting with the predominant expression of total NACP mRNA in brain with a slight expression in placenta. These results suggest differential regulation of NACP RNA splicing among tissues. (C) 1994 Academic Press, Inc.