Tissue distribution, biochemical properties, and transmission of mouse type A AApoAII amyloid fibrils.
In mouse strains with the amyloidogenic apolipoprotein A-II (ApoA-II) gene (Apoa2c), the type C ApoA-II protein (APOAIIC) associates to form amyloid fibrils AApoAII(C) that lead to development of early onset and systemic amyloidosis with characteristic heavy amyloid deposits in the liver and spleen. We found age-associated heavy deposition of amyloid fibrils [AApoAII(A)] composed of type A ApoA-II protein (APOAIIA) in BDF1 and C57BL/6 mice reared at one of our institutes. AApoAII(A) fibrils were deposited in the intestine, lungs, tongue, and stomach but not in the liver or spleen. AApoAII(A) fibrils were isolated, and morphological, biochemical, and structural characteristics distinct from those seen in AApoAII(C) and mouse AA amyloid fibrils were found. Transmission electron and atomic force microscopy showed that the majority of isolated AApoAII(A) amyloid fibrils featured fine, protofibril-like shapes. AApoAII(A) fibrils have a much weaker affinity for thioflavine T than for AApoAII(C), whereas APOAIIA protein contains less of the beta-pleated sheet structure than does APOAIIC. The injection of AApoAII(A) fibrils induced amyloid deposition in C57BL/6 and DBA2 mice (Apoa2a) as well as in R1.P1-Apoa2c mice (Apoa2c), but AApoAII(A) induced more severe amyloidosis in Apoa2a strains than in the Apoa2c strain. It was found that AApoAII(A) fibrils isolated from mice with mildly amyloidogenic APOAIIA protein have distinct characteristics. Induction of amyloidosis by heterologous amyloid fibrils clearly showed interactions between amyloid protein monomers and fibrils having different primary structures.
Korenaga
Tatsumi
T
Department of Aging Biology, Institute on Aging and Adaptation, Shinshu University Graduate School of Medicine, Matsumoto, Japan.
Fu
Xiaoying
X
Xing
Yanming
Y
Matsusita
Takatoshi
T
Kuramoto
Kazunao
K
Syumiya
Seigo
S
Hasegawa
Kazuhiro
K
Naiki
Hironobu
H
Ueno
Masaki
M
Ishihara
Tokuhiro
T
Hosokawa
Masanori
M
Mori
Masayuki
M
Higuchi
Keiichi
K
D000483:Alleles; D000682:Amyloid / Q000096:biosynthesis* / Q000737:chemistry; D000818:Animals; D016633:Apolipoprotein A-II / Q000737:chemistry*; D004305:Dose-Response Relationship, Drug; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D018625:Microscopy, Atomic Force; D008854:Microscopy, Electron; D017433:Protein Structure, Secondary; D013997:Time Factors; D014018:Tissue Distribution
D000682:Amyloid; D016633:Apolipoprotein A-II