title: Transgenic mice overexpressing both amyloid beta-protein and perlecan in pancreatic acinar cells.
abstract: Heparan sulfate proteoglycans such as perlecan are thought to facilitate amyloid fibril formation. Tg3695 mice overexpress perlecan core protein in many tissues including the brain and pancreas. Tg13592 mice overexpress the signal plus 99-amino acid carboxyl terminal sequences (C99) of amyloid beta-protein precursor in multiple tissues and develop amyloid deposits in the pancreas. To investigate a role of perlecan in beta-amyloidosis, we established doubly transgenic mice by crossing the two lines of transgenic mice. The expression levels of the two transgenes remained unchanged in the brain and pancreas and the doubly transgenic mice did not develop amyloid deposits in the brain up to 19-months of age. Amyloid load detected by thioflavine S in the pancreas of the doubly transgenic mice was not significantly different from that in the transgenic littermates expressing only C99. Amyloid load in the pancreas increased during aging. We found a positive correlation between the Abeta-immunoreactive (non-fibrillar and fibrillar) and thioflavine S-positive (fibrillar) Abeta deposits in the single (C99) but not doubly transgenic mice. Our results suggest that perlecan does not independently influence amyloid formation in the pancreas of the transgenic mice and that there may be other factors that may modulate amyloid formation together with perlecan.
authors.affiliation: Department of Genetics, Schools of Medicine and Dentistry, University of Alabama at Birmingham, Birmingham, Alabama, USA. fukuchi@uab.edu
authors.forename: K
authors.initials: K
authors.lastname: Fukuchi
authors.forename: M
authors.initials: M
authors.lastname: Hart
authors.forename: Z
authors.initials: Z
authors.lastname: Yan
authors.forename: J R
authors.initials: JR
authors.lastname: Hassell
authors.forename: L
authors.initials: L
authors.lastname: Li
mesh_terms: D000375:Aging / Q000378:metabolism; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D016564:Amyloid beta-Protein Precursor / Q000378:metabolism; D000686:Amyloidosis / Q000378:metabolism*; D000818:Animals; D015153:Blotting, Western; D001923:Brain Chemistry; D003433:Crosses, Genetic; D019812:Heparan Sulfate Proteoglycans / Q000378:metabolism*; D007150:Immunohistochemistry; D051379:Mice; D008822:Mice, Transgenic; D010179:Pancreas / Q000166:cytology* / Q000378:metabolism*; D019076:Transgenes
chemical_list: D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; D019812:Heparan Sulfate Proteoglycans; C071927:perlecan