Amyloid resistance in A/J mice is determined by a single gene

Wohlgethan, J R; Cathcart, Edgar S.

doi:10.1038/278453a0

Cited by 22 publications

(15 citation statements)

References 4 publications

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“…A similar factor has been demonstrated in A/J mice (Wohlgethan and Cathcart 1980), a strain known for its resistance to arnyloid induction (Wohlgethan and Cathcart 1979). Passive transfer experiments with A/J mice significantly reduce the induction period for AA amylsid deposition from months to days (Wohlgethan and Cathcart 1980).…”

Section: Inflammation and Aposaasupporting

confidence: 61%

From arthritis to Alzheimer's disease: current concepts on the pathogenesis of amyloidosis

Kisilevsky¹

1987

Can. J. Physiol. Pharmacol.

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Amyloid is a generic term referring to a group of diverse but specific extracellular protein deposits which all have common morphologic properties, staining characteristics, and x-ray diffraction and infrared spectra. This review considers the new classification of amyloids, based on the underlying peptides forming the protein fibril, and their diversity. The pathogenesis of inflammation-associated amyloid and its relationship to high density lipoprotein metabolism is examined in detail. The lessons learned from models of inflammation-associated amyloid are extended to the other amyloids (e.g., Alzheimer's disease), and potential reasons for the common structural properties of all amyloids are explored.

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Section: Inflammation and Aposaasupporting

confidence: 61%

From arthritis to Alzheimer's disease: current concepts on the pathogenesis of amyloidosis

Kisilevsky¹

1987

Can. J. Physiol. Pharmacol.

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“…This variability may partly be due to the primary structure of the precursor protein, as in AA-amyloid-resistant CE/J mice, which synthesize nonamyloidogenic acute phase SAA isoforms [52]. However, the primary structure of SAA may not be the only factor contributing to amyloid susceptibility [56]. Differences in the binding and endocytosis of HDL SAA by cells of the RES may also be an influence.…”

Section: Introductionmentioning

confidence: 98%

Comparison of the binding and endocytosis of high-density lipoprotein from healthy (HDL) and inflamed (HDL SAA ) donors by murine macrophages of four different mouse strains

Röcken

Kisilevsky

1998

Virchows Archiv

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Serum amyloid A (SAA) is a plasma acute phase protein and the precursor of the AA-fibril protein deposited in AA-amyloidosis. SAA is bound mainly to high-density lipoproteins (HDL(SAA)). Previous investigations have demonstrated that peritoneal macrophages (mO) from mice are capable of binding and endocytosing HDL(SAA). This observation may indicate a pathway by which SAA enters the mO and where its intracellular metabolism may be followed by degradation and/or amyloidogenesis. Since binding and internalization defects of lipoproteins may be associated with different diseases, it is possible that mouse strain susceptibility to amyloidosis is associated with qualitative differences in the binding and internalization of HDL(SAA). To test this hypothesis a series of binding and internalization experiments was performed in vitro with mO from four different mouse strains, CD-1, A/J, C57BL/6J and C3H/HeJ, which differ in their susceptibility to AA-amyloidosis. Using colloidal gold-labelled lipoproteins, it was evident by light and electron microscopy that mO from all four mouse strains are capable of binding and internalizing HDL (without SAA) and HDL(SAA). HDL and HDL(SAA) were found in such compartments of the receptor-mediated pathway as coated pits, coated vesicles, endosomes and multivesicular bodies and in lipid droplets; no qualitative differences were observed. Therefore, it is unlikely that a defect in binding and uptake of HDL(SAA) is related to the different susceptibilities of these mouse strains to develop AA-amyloidosis. However, the results do not exclude the possibility that differences in the intracellular processing of SAA following endocytosis of HDL(SAA) is involved in this differing susceptibility.

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“…Mice of the C57BL/6 and CBA/J strains are known to develop reactive AA amyloidosis within 15-21 days of casein treatment while mice of the A/J strain take more than 40 days to develop AA amyloidosis and are thus considered resistant to the development of amyloidosis. Genetic analysis has suggested that the relative resistance to the development of reactive AA amyloidosis seen in mice of the A/J strain is controlled by a single autosomal dominant gene [9][10][11].…”

Section: Introductionmentioning

confidence: 99%

Degradation of Amyloid A Precursor Protein SAA by Macrophage Cell Lines Obtained from Amyloid Resistant and Susceptible Strains of Mice

et al. 1997

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1997;45:354-360 Reactive AA amyloidosis can be induced in mice in a model of sustained inflammation following daily casein subcutaneous injections. However, the development of AA amyloidosis is known to vary in different strains of mice. The C57BL/6 strain is susceptible to the development of amyloidosis while the A/J strain is resistant. The degradation of purified serum amyloid A (SAA) protein by human monocytes as well as by mouse macrophages has been shown. The resistance/susceptibility of different mouse strains to the development of systemic amyloidosis may therefore be related to a difference in the ability of macrophages to degrade SAA. The authors have used bone marrow-derived macrophage cell lines obtained from susceptible C57BL/6 (ANA-1) and resistant A/J (A/J 10) mouse strains to compare their ability to degrade HDL-SAA in vitro. Cells were incubated with HDL-SAA for up to 72 h and the culture medium was analysed by SDS-PAGE to determine the rate of SAA degradation by the macrophages. The A/J 10 cells (resistant) were found to initiate a constant HDL-SAA degradation promptly whereas ANA-1 cells (susceptible) showed an intermittent block in the degradation of the precursor. Activation of macrophages by lipopolysaccharide (LPS) or interferon-g (IFN-g) hampered the precursor degradation suggesting that the activation process may favour extracellular accumulation of the precursor leading to a partial degradation and fibril formation.

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Amyloid resistance in A/J mice is determined by a single gene

Cited by 22 publications

References 4 publications

From arthritis to Alzheimer's disease: current concepts on the pathogenesis of amyloidosis

From arthritis to Alzheimer's disease: current concepts on the pathogenesis of amyloidosis

Comparison of the binding and endocytosis of high-density lipoprotein from healthy (HDL) and inflamed (HDL SAA ) donors by murine macrophages of four different mouse strains

Degradation of Amyloid A Precursor Protein SAA by Macrophage Cell Lines Obtained from Amyloid Resistant and Susceptible Strains of Mice

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