Accumulation of Amyloid β Protein in Transgenic Mice

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