Transmission of amyloidosis in offspring of mice with AApoAII amyloidosis.
Pre-existing amyloid fibrils can induce further polymerization of endogenous precursor proteins in vivo. Thus, transmission of amyloid fibrils (AApoAII) may induce a conformational change in endogenous apolipoprotein A-II and accelerate amyloid deposition in mouse senile amyloidosis. To characterize transmissibility, we examined amyloidosis in the offspring of AApoAII-injected mother mice that possessed the amyloidogenic Apoa2(c) allele of the apolipoprotein A-II gene. At 4 months of age, amyloid deposits were detected in the intestines of offspring born from and nursed by amyloid fibril-injected mothers, with intensity of deposition increasing thereafter. No amyloid deposits were detected in the offspring of noninjected control mothers. Accelerated amyloidosis was also observed in offspring born from mothers without injection but nursed by amyloid fibril-injected mothers. However, this was not observed in offspring born from amyloid fibril-injected mothers but nursed by control mothers. This fostering excluded vertical transmission through the placenta, suggesting the presence of factors that accelerate amyloidosis during the nursing period. In addition, milk obtained from amyloid fibril-injected mothers induced AApoAII amyloidosis in young mice, and transmission electron microscopy detected noodle-like amyloid fibrils in milk of amyloid fibril-injected mothers. These results provide important insight into the etiology and pathogenesis of amyloid diseases.
Korenaga
Tatsumi
T
Department of Aging Biology, Institute on Aging and Adaptation, Shinshu University Graduate School of Medicine, Asahi 3-1-1, Matsumoto 390-8621, Japan.
Yan
Jingmin
J
Sawashita
Jinko
J
Matsushita
Takatoshi
T
Naiki
Hironobu
H
Hosokawa
Masanori
M
Mori
Masayuki
M
Higuchi
Keiichi
K
Fu
Xiaoying
X
D000483:Alleles; D000682:Amyloid / Q000032:analysis / Q000633:toxicity* / Q000648:ultrastructure; D000686:Amyloidosis / Q000139:chemically induced / Q000209:etiology* / Q000473:pathology; D000818:Animals; D016633:Apolipoprotein A-II / Q000235:genetics / Q000378:metabolism / Q000633:toxicity*; D005260:Female; D018445:Infectious Disease Transmission, Vertical; D008297:Male; D051379:Mice; D008817:Mice, Mutant Strains; D008892:Milk / Q000378:metabolism; D014556:Urine
D000682:Amyloid; D016633:Apolipoprotein A-II