Specific Deposition of Serum Amyloid A Protein 2 in the Mouse

Shiroo, Masahiro; Kawahara, Ei; Nakanishi, Isao; Migita, Shunsuke

doi:10.1111/j.1365-3083.1987.tb02307.x

Cited by 65 publications

(49 citation statements)

References 22 publications

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“…SAA proteins are acute-phase reactants that originate in the liver and are liberated into the plasma after cytokine stimulation Vogel and Sipe, 1982). In the mouse, the two acute-phase SAA proteins are SAA1.1 and SAA2.1; during inflammation-associated amyloid formation, only the SAA1.1 isoform is deposited into amyloid (Meek et al, 1986;Shiroo et al 1987). The CE/J mouse contains a single SAA gene, SAA2.2, which seems to be a composite of the SAA1.1 and SAA2.1 genes .…”

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confidence: 99%

Expression of Mouse Apolipoprotein SAA1.1 in CE/J Mice: Isoform-Specific Effects on Amyloidogenesis

Zhu

Guo

et al. 2000

Laboratory Investigation

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Kentucky SUMMARY:Amyloid A (AA) amyloid deposition in mice is dependent upon isoform-specific effects of the serum amyloid A (SAA) protein. In type A mice, SAA1.1 and SAA2.1 are the major apolipoprotein-SAA isoforms found on high-density lipoproteins. During inflammation, both isoforms are increased 1000-fold, but only SAA1.1 is selectively deposited into amyloid fibrils. Previous studies showed that the CE/J mouse strain is resistant to amyloid induction. This resistance is not due to a deficiency in SAA synthesis, but is probably related to the unusual SAA isoform present. The CE/J mouse has a single acute-phase SAA protein (SAA2.2), which is a composite of the SAA1.1 and SAA2.1, with an amino terminus similar to the nonamyloidogenic SAA2.1. Recently, genetic experiments suggested that the SAA2.2 isoform might provide protection from amyloid deposition. To determine the amyloidogenic potential of the CE/J mouse, we generated SAA adenoviral vectors to express the various isoforms in vitro and in vivo. Purified recombinant SAA proteins demonstrated that SAA1.1 was fibrillogenic in vitro, whereas SAA2.2 was unable to form fibrils. Incubation of increasing concentrations of the nonamyloidogenic SAA2.2 protein with the amyloidogenic SAA1.1 did not inhibit the fibrillogenic nature of SAA1.1, or alter its ability to form extensive fibrils. Injection of the mouse SAA1.1 or SAA2.2 adenoviral vectors into mice resulted in isoform-specific expression of the SAA proteins. Amyloid induction after viral expression of the SAA1.1 protein resulted in the deposition of amyloid fibrils in the CE/J mouse, whereas SAA2.2 expression had no effect. Similar expression of the SAA2.2 protein in C57BL/6 mice did not alter amyloid deposition. These data demonstrate that the failure of the CE/J mouse to deposit amyloid is due to the structural inability of the SAA2.2 to form amyloid fibrils. This mouse provides a unique system to test the amyloidogenic potential of altered SAA proteins and to determine the important structural features of the protein. (Lab Invest 2000, 80:1797-1806.

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Expression of Mouse Apolipoprotein SAA1.1 in CE/J Mice: Isoform-Specific Effects on Amyloidogenesis

Zhu

Guo

et al. 2000

Laboratory Investigation

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“…The function of the different isoforms is not clear, and in humans it has been reported that there is no disease-specific pattern of SAA isoforms in dis- eases including amyloidosis. On the other hand, only SAA 2 , which is one of the isoforms , seems to be the precursor of AA in the mouse [15]. Alsemgeest [1] reported that bovine SAA has some specific isoform expression patterns, and the sera obtained from cows with different diseases showed variable ratios of the isoforms, and furthermore, only one isoform was detectable in the serum of a cow suffering from spontaneous AA-amyloidosis.…”

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Serum Amyloid A and Haptoglobin Levels in Bovine Amyloidosis

Takahashi

Uzuka

Tanabe

et al. 2007

The Journal of Veterinary Medical Science

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ABSTRACT. Serum amyloid A (SAA) and haptoglobin (Hp) levels were determined in 25 cows suffering from amyloidosis. SAA levels in cows with amyloidosis ranged between < 0.3 and 225.8 µg/ml, with a median level of 105.1 µg/ml, and Hp levels ranged between < 20 and 1860 µg/ml, with a median level of 950 µg/ml. These levels were significantly higher than the levels observed in healthy cows (SAA levels ranged from < 0.3 to 13.5 µg/ml, with median of 1.4 µg/ml, and Hp levels were undetectable in all cases), but were not significantly different from the levels observed in control cows with chronic inflammation. There was a significant correlation between SAA and Hp levels in cows with chronic inflammation , but not in cows with amyloidosis. It was concluded that the serum SAA levels in cows with amyloidosis might be changed by some factor other than inflammation. KEY WORDS: amyloidosis, haptoglobin, serum amyloid A.

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“…The disease is characterized by the deposition of amyloid fibrils, which are derived from A-SAA [11], in the major organs of the body. It has been demonstrated in mouse that the amyloid fibrils are principally derived from the A-SAA2 isoform [22,24]. Given that amyloidosis depends on high circulating levels of a single pathogenic protein, A-SAA2, a reduction in its concentration could form the basis of a therapeutic model.…”

Section: Resultsmentioning

confidence: 99%

“…The mouse is a useful experimental model for both secondary amyloidosis [22] and atherosclerosis. The mouse SAA gene family comprises three A-SAA genes (Saa1, Saa2 and Saa3), a constitutively expressed gene (Saa5 ) and a pseudogene (Saa4 ).…”

Section: Introductionmentioning

confidence: 99%

“…All five genes map within a 45 kb cluster on chromosome 7 [23]. There is strong evidence that in mouse the specific precursor of AA in secondary amyloid plaques is the A-SAA2 isoform [22,24]. Therefore it is likely that a significant reduction in circulating A-SAA2 levels would reduce or abolish AA deposition, and several strategies to achieve this may be considered.…”

Section: Introductionmentioning

confidence: 99%

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Efficient In Vitro Cleavage of Mouse Acute Phase Serum Amyloid A mRNA Mediated by a Synthetic Hammerhead Ribozyme

Gaughan

Whitehead

1997

Scand J Immunol

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Gaughan DJ, Whitehead AS. Efficient In Vitro Cleavage of Mouse Acute Phase Serum Amyloid A mRNA Mediated by a Synthetic Hammerhead Ribozyme. Scand J Immunol 1997;46:51-58 The authors designed a hammerhead ribozyme, mRibSAA2, to cleave the mRNA for mouse acute phase serum amyloid A 2 (A-SAA2), a major acute phase protein that is massively induced during inflammation and that is deposited as fibrils during secondary amyloidosis. Using computer based secondary structure analysis, a GUC triplet (nucleotides 408-410) on a predicted stem loop in A-SAA2 mRNA was chosen as the target site for mRibSAA2. The ribozyme was tested in vitro and gave efficient and specific magnesium-dependent cleavage of mouse A-SAA2 mRNA into the expected fragments of 197 and 425 bases. The authors also demonstrated that the ribozyme retains cleavage activity over several hours. The use of the mRibSAA2 ribozyme as a research tool and possible therapeutic agent in mouse models of amyloidosis is discussed.

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Specific Deposition of Serum Amyloid A Protein 2 in the Mouse

Cited by 65 publications

References 22 publications

Expression of Mouse Apolipoprotein SAA1.1 in CE/J Mice: Isoform-Specific Effects on Amyloidogenesis

Expression of Mouse Apolipoprotein SAA1.1 in CE/J Mice: Isoform-Specific Effects on Amyloidogenesis

Serum Amyloid A and Haptoglobin Levels in Bovine Amyloidosis

Efficient In Vitro Cleavage of Mouse Acute Phase Serum Amyloid A mRNA Mediated by a Synthetic Hammerhead Ribozyme

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