Accumulation of amyloid β protein in transgenic mice

Carboxyl-terminal fragments of beta amyloid precursor protein (beta APP) were expressed in mice under the transcriptional control of an ubiquitous promoter system, based upon a chicken beta-acrin (beta A) promoter combined with cytomegalovirus (CMV) enhancer to obtain a systemic overproduction of amyloid beta protein (beta P). Three transgene constructs were designed to encode signal peptide and carboxyl-terminal 99 amino acid residues to beta APP (NOR-beta), methionine and C-terminal 103 amino acid residues of beta APP (Delta NOR-beta), and methionine and C-terminal 103 amino acid residues with KM-NL substitution of beta APP (Delta NL-beta). Although the transcriptional mRNA level and post-translational protein level from transgenes showed the same expression pattern, both the expression of A beta and distribution of A beta deposits were completely different among these strains. In NOR-beta mice, considerable amounts of A beta were detected in plasma and A beta deposits were observed in the pancreas. Brain A beta deposits and small amounts of plasma A beta were recognized in Delta NL-beta. These findings indicate that tissue specific processing and transgene constructs are major facters to determine the distribution of A beta deposits. (C) 1998 Elsevier Science Inc.