Amyloid-Enhancing Factor: Production and Response in Amyloidosis-Susceptible and -Resistant Mouse Strains

Abstract

Genetic variations in the development of casein-induced amyloidosis exist among inbred strains of mice: CBA/J and C57BL/6J mice are susceptible, while A/J strain mice are resistant to this disease. Amyloidosis is usually induced by daily injections of an inflammatory stimulus for 2-3 wk. The deposition of amyloid in experimental animals can be accelerated by injection of a material called amyloid-enhancing factor (AEF); when injected concomitantly with an inflammatory stimulus, AEF provokes appearance of amyloidosis as early as 2 days after injection. AEF is extracted from amyloid laden or from normal organs (although in small amount). Our studies were designed to determine if the resistance to amyloidosis seen in A/J mice was either due to a lack of AEF production or to an inability of these mice to respond to AEF. A standard source of CBA/J-derived AEF facilitated the development of amyloidosis in the organs of both the susceptible (CBA/J, C57BL/6J) and the resistant A/J mice. On the contrary, amyloidosis was only induced in susceptible CBA/J hosts when material derived from susceptible (CBA/J, C57BL/6J) animals was injected. CBA/J mice injected with A/J-derived AEF preparation did not develop amyloidosis. These results thus suggest that the determination of resistance or susceptibility to secondary amyloidosis could operate at the level of AEF production.

Age delays thyroglobulin progression towards dense lysosomes in the cream hamster thyroid

“…Spontaneous amyloidosis occurs in aging rodents, in Syrian gold hamsters (Dontenwill et al 1960;Swaen and van Haelst 1960) and in different strains of mice. In mice, the deposit was typed as A amyloid and was concomitant with inflammatory cell infiltration (Gervais et al 1988, Maniratunga et al 1993, which is not the case in hamsters. Female mice appear more susceptible and estrogens promote the advent of amyloid at earlier ages (Boonyanit 1966).…”

apo‐SAA1/apo‐SAA2 Isotype Ratios during Casein‐ and Amyloid‐Enhancing‐Factor‐Induced Secondary Amyloidosis in A/J and C57BL/6J Mice

“…AEF appears to be produced late in the pre-amyloid phase, just preceding the deposition of amyloid fibrils in the organs, and is thought to accelerate the deposition of amyloid fibrils in mice [14,21,42]. Furthermore, the importance of AEF in the course of amyloidosis induction was emphasized in previous studies demonstrating that the amyloidosis-susceptible C57BL/6J and CBA/J mouse strains produced AEF during a sustained inflammatory stimulus while the resistant A/J mouse strain did not [10]. This resistance seen in A/J mice is not caused by a defect in SAA2 mRNA synthesis as seen in young SJL mice [44], since apoSAA2 could be found in HDL serum preparations following casein injections.…”

“…Preparation ofthe AEE. AEF was prepared from the spleens by extraction in ice-cold 30% glycerol-10 mM Tris, pH 7.5, as previously described [10].…”

“…Indeed, elevated amounts of SAA are found in both resistant A/J and susceptible C57BL/6J and CBA/J mice [29]. Resistance seen in A/J mice was linked to their inability to produce the 'amyloidenhancing factor' (AEF) during a regular course of amyloidosis induction with casein injections [10].…”

Resistance to Secondary Amyloidosis in A/J Mice is Not Significantly Associated with Allelic Variants Linked to the Serum Amyloid A Gene Cluster

“…The hypothesis tested in the present study was whether allelic structural variants at the 'amyloidogenie' SAA2 locus, or other variants residing in the SAA gene cluster, confer resistance to secondary amyloidosis in A/J mice. Although the results of Gervais et al [19] suggest that A/J amyloid resistance may operate at the level of amyloid-enhancing factor (AEF) production, a number of studies support the suggestion that variant SAA genes can provide resistance to secondary amyloidosis. Rats cannot generally be induced to accumulate amyloid fibrils under experimental conditions [20,21].…”