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Transmission of mouse senile amyloidosis
1Department of Aging Angiology, Research Center on Aging and Adaptation, Shinshu University School of Medicine, Matsumoto, Japan.
Summary:
In mouse senile amyloidosis, apolipoprotein A-II polymerizes into amyloid fibrils (AApoAII) and deposits systemically. Peripheral injection of AApoAII fibrils into young mice induces systemic amyloidosis (Higuchi et al, 1998). We isolated AApoAII amyloid fibrils from the livers of old R1.P1-Apoa2(c) mice and injected them with feeding needles into the stomachs of young R1.P1-Apoa2(c) mice for 5 consecutive days. After 2 months, all mice had AApoAII deposits in the lamina propria of the small intestine. Amyloid deposition extended to the tongue, stomach, heart, and liver at 3 and 4 months after feeding. AApoAII suspended in drinking water also induced amyloidosis. Amyloid deposition was induced in young mice reared in the same cage for 3 months with old mice who had severe amyloidosis. Detection of AApoAII in feces of old mice and induction of amyloidosis by the injection of an amyloid fraction of feces suggested the propagation of amyloidosis by eating feces. Here, we substantiate the transmissibility of AApoAII amyloidosis and present a possible pathogenesis of amyloidosis, ie, oral transmission of amyloid fibril conformation, where we assert that exogenous amyloid fibrils act as templates and change the conformation of endogenous amyloid protein to polymerize into amyloid fibrils.
Insights
This study shows that amyloidosis in mice, caused by apolipoprotein A-II (AApoAII) amyloid fibrils, can be transmitted orally. Ingesting AApoAII fibrils or feces from affected mice induced amyloidosis in healthy mice, suggesting a contagious mechanism.
Area of Science:
- Biochemistry
- Pathology
- Immunology
Background:
- Senile amyloidosis in mice involves the systemic deposition of apolipoprotein A-II amyloid fibrils (AApoAII).
- Previous research demonstrated that peripheral injection of AApoAII fibrils induces systemic amyloidosis in young mice.
Purpose of the Study:
- To investigate the transmissibility of AApoAII amyloidosis through oral ingestion.
- To explore the potential pathogenesis of amyloidosis via oral transmission of amyloid fibril conformation.
Main Methods:
- Isolation of AApoAII amyloid fibrils from the livers of old R1.P1-Apoa2(c) mice.
- Oral administration of AApoAII fibrils or AApoAII suspended in drinking water to young mice.
- Caging young mice with old mice exhibiting severe amyloidosis.
- Analysis of AApoAII presence in feces and its amyloidosis-inducing potential.
Main Results:
- Oral administration of AApoAII fibrils induced AApoAII deposits in the small intestine within 2 months, spreading to other organs by 4 months.
- Amyloidosis was also induced by AApoAII in drinking water and by cohabitation with affected mice.
- Detection of AApoAII in feces and its ability to induce amyloidosis suggested fecal-oral transmission.
Conclusions:
- AApoAII amyloidosis is transmissible through oral routes, including ingestion of feces.
- Exogenous amyloid fibrils may act as templates, inducing conformational changes in endogenous proteins to promote polymerization and amyloid formation.