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Transgenic mice overexpressing both amyloid ß-protein and perlecan in pancreatic acinar cells K. Fukuchi1, M. Hart1, Z. Yan1, J.R. Hassell2 and L. Li3 Departments of 1Genetics and 3Medicine,
Schools of Medicine and Dentistry, University of Alabama at Birmingham,
Birmingham, Alabama and 2Shriners Hospitals for Children, Tampa,
Florida, USA Offprint requests to: Dr. Ken-ichiro Fukuchi M.D., Ph.D., Associate Professor, UAB Department of Gentics, KHGB 640B, 720 South 20th Street, Birmingham, AL 35294-0024, USA. Fax: (205) 975-5519. e-mail: fukuchi@uab.edu
Summary. 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 ß-protein precursor in multiple tissues and develop amyloid deposits in the pancreas. To investigate a role of perlecan in ß-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 Aß-immunoreactive (non-fibrillar and fibrillar) and thioflavine S-positive (fibrillar) Aß 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. Histol. Histopathol. 19, 845-852 (2004) Key words: Amyloid,
Perlecan, Transgenic Mice, Pancreas |