Transmission of Mouse Senile Amyloidosis

Xing, Yanming; Nakamura, Akihiro; Chiba, Takuya; Kogishi, Kumiko; Matsushita, Takatoshi; Fu, Li; Guo, Zhanjun; Hosokawa, Masanori; Mori, Masayuki; Higuchi, Kenichi

doi:10.1038/labinvest.3780257

Cited by 97 publications

(79 citation statements)

References 31 publications

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“…In this study, we showed that the fecal fraction from a cheetah with amyloidosis had AA amyloid fibrils and possessed high transmissibility. In mouse AApoAII amyloidosis, regarded recently as another transmissible amyloidosis (5-7), we also demonstrated that the feces could serve as an agent to induce amyloidosis in recipient mice (31). These results shed new light on the etiology involved in the high incidence of AA amyloidosis in cheetahs.…”

Section: Discussionmentioning

confidence: 72%

Fecal transmission of AA amyloidosis in the cheetah contributes to high incidence of disease

Zhang

Une

et al. 2008

Proc. Natl. Acad. Sci. U.S.A.

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AA amyloidosis is one of the principal causes of morbidity and mortality in captive cheetahs (Acinonyx jubatus), which are in danger of extinction, but little is known about the underlying mechanisms. Given the transmissible characteristics of AA amyloidosis, transmission between captive cheetahs may be a possible mechanism involved in the high incidence of AA amyloidosis. In this study of animals with AA amyloidosis, we found that cheetah feces contained AA amyloid fibrils that were different from those of the liver with regard to molecular weight and shape and had greater transmissibility. The infectious activity of fecal AA amyloid fibrils was reduced or abolished by the protein denaturants 6 M guanidine⅐HCl and formic acid or by AA immunodepletion. Thus, we propose that feces are a vehicle of transmission that may accelerate AA amyloidosis in captive cheetah populations. These results provide a pathogenesis for AA amyloidosis and suggest possible measures for rescuing cheetahs from extinction.feces ͉ transmissibility

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Section: Discussionmentioning

confidence: 72%

Fecal transmission of AA amyloidosis in the cheetah contributes to high incidence of disease

Zhang

Une

et al. 2008

Proc. Natl. Acad. Sci. U.S.A.

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111

107

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“…[8][9][10] Previously, we have described prion-like transmission of AApoAII amyloidosis in which intravenous, peripheral and oral injection of AApoAII amyloid fibrils markedly accelerated amyloid deposition in young R1.P1-Apoa2 c mice. 11,12 We also observed that young R1.P1-Apoa2 c mice showed rapid onset of amyloidosis when they share cages with old R1.P1-Apoa2 c mice with severe amyloid deposits. Furthermore, offspring nursed by amyloidosis-induced mothers showed early development of amyloidosis.…”

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confidence: 62%

“…Furthermore, offspring nursed by amyloidosis-induced mothers showed early development of amyloidosis. 12,13 The propagation of amyloidosis among mice probably occurred through the consumption of AApoAII fibrils contained in feces and milk. Injection of AApoAII fibrils also induced amyloidosis in less-amyloidogenic mouse strains with Apoa2 a or Apoa2 b alleles.…”

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confidence: 99%

Amyloidosis in transgenic mice expressing murine amyloidogenic apolipoprotein A-II (Apoa2)

Yao

et al. 2007

Laboratory Investigation

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In mice, apolipoprotein A-II (apoA-II) self-associates to form amyloid fibrils (AApoAII) in an age-associated manner. We postulated that the two most important factors in apoA-II amyloidosis are the Apoa2 c allele, which codes for the amyloidogenic protein APOA2C (Gln5, Ala38) and transmission of amyloid fibrils. To characterize further the contribution of the Apoa2 c allele to amyloidogenesis and improve detection of amyloidogenic materials, we established transgenic mice that overexpress APOA2C protein under the cytomegalovirus (CMV) immediate early gene (CMV-IE) enhancer/ chicken b promoter. Compared to transgene negative (Tg À/À ) mice that express apoA-II protein mainly in the liver, mice homozygous (Tg þ / þ ) and heterozygous (Tg þ /À ) for the transgene express a high level of apoA-II protein in many tissues. They also have higher plasma concentrations of apoA-II, higher ratios of ApoA-II/apolipoprotein A-I (ApoA-I) and higher concentrations of high-density lipoprotein (HDL) cholesterol. Following injection of AApoAII fibrils into Tg þ / þ mice, amyloid deposition was observed in the testis, liver, kidney, heart, lungs, spleen, tongue, stomach and intestine but not in the brain. In Tg þ / þ mice, but not in Tg À/À mice, amyloid deposition was induced by injection of less than 10 À8 mg AApoAII fibrils. Furthermore, deposition in Tg þ / þ mice occurred more rapidly and to a greater extent than in Tg À/À mice. These studies indicate that increased levels of APOA2C protein lead to earlier and greater amyloid deposition and enhanced sensitivity to the transmission of amyloid fibrils in transgenic mice. This transgenic mouse model should prove valuable for studies of amyloidosis.

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“…This finding is in contrast to the pattern of AA deposition in other species of small ruminants, as well as horses and experimental rodents, where amyloid was found to be most pronounced in spleen, liver, adrenal glands, and gastrointestinal tract. 9,11,22,40,45,47 This difference in tissue distribution of AA amyloid among animal species suggests that particular host factors, e.g., accessory molecules such as proteoglycans that codeposit with the amyloidogenic protein, 37 may be involved in this phenomenon. Alternatively, the presence of multiple, SAA isoforms in sheep and goats, such as found in mice, cows, and humans, may account for organ selectivity.…”

Section: Discussionmentioning

confidence: 99%

Pathology of AA Amyloidosis in Domestic Sheep and Goats

Ménsua

2003

Veterinary Pathology

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Abstract. We describe the main pathologic changes in small ruminants affected by AA amyloidosis, together with the partial sequence of the protein involved. Twenty-one sheep and one goat were selected for presenting macroscopic kidney lesions compatible with systemic amyloidosis. Available tissue samples were studied by histologic, immunopathologic, and ultrastructural means. Renal lesions were characterized grossly by pale cortical surfaces with scattered, miliary, whitish-yellow foci and on cut cortical surfaces by straight, whitish-yellow striations. Gangrenous pneumonia was observed in 16 out of 21 affected sheep (76.2%), although other chronic inflammations were also observed. Amyloid was detected in all grossly affected kidneys using Congo red staining, lesions being most remarkable in glomeruli, affecting 95.5% of animals studied. Congophilic deposits were also observed in intertubular interstitium (68.2%) and medulla (57.1%). All amyloid-affected animals presented proximal convoluted tubule lesions, mostly characterized by an increase in diameter and by hyaline granular degeneration that were responsible for the macroscopic appearance of the kidney. Histologically, amyloid was also seen in blood vessels, spleen, liver, lymph nodes, gastrointestinal tract, and adrenal glands. All amyloid deposits demonstrated greenish-yellow birefringence with polarized light, and the antisera prepared against goat amyloid extracts specifically reacted with birefringent congophilic deposits of both sheep and goats. Ultrastructurally, these deposits were formed by masses of straight, nonbranching fibrils located predominantly in the basement membranes of glomerular capillaries and in the mesangium. Partial sequence of the protein in sheep and goats indicated a high degree of homology with the previously reported sequence of sheep Serum Amyloid A.

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Transmission of Mouse Senile Amyloidosis

Cited by 97 publications

References 31 publications

Fecal transmission of AA amyloidosis in the cheetah contributes to high incidence of disease

Fecal transmission of AA amyloidosis in the cheetah contributes to high incidence of disease

Amyloidosis in transgenic mice expressing murine amyloidogenic apolipoprotein A-II (Apoa2)

Pathology of AA Amyloidosis in Domestic Sheep and Goats

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