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

Abstract

A/J mice are resistant while C57BL/6J are susceptible to casein-induced secondary amyloidosis. One mechanism responsible for this phenotypic expression of resistance/susceptibility was shown to operate at the level of production of the 'amyloid-enhancing factor' (AEF). AEF and processing of the apo-SAA protein appear almost concomitantly during amyloidogenesis. In order to determine if AEF played a role in the processing of the apo-SAA protein, three major parameters (apo-SAA1/apo-SAA2 ratios, level of AEF, and fibril formation) were determined during casein-induced secondary amyloidosis. Kinetics of AEF production and serum levels of the two major apo-SAA isotypes were compared in A/J and C57BL/6J animals. Both strains showed equal relative amounts of the two isotypes after seven, 15 and 21 casein injections, irrespective of the fact that the A/J strain had no detectable level of AEF and no amyloid deposition; while C57BL/6J mice had a high AEF level and were amyloidotic after 15 and 21 injections. An increased apo-SAA1/apo-SAA2 ratio due to a decrease in apo-SAA2 was noted after 38 days of casein injections when both strains had extensive deposits of amyloid fibrils. Involvement of AEF as an effector molecule was determined by following the ratio of the two major serum apo-SAA isotypes and fibril formation during an accelerated protocol of amyloid induction in C57BL/6J animals. AEF had no direct effect on apo-SAA isotype ratios in the serum.