Lung, ileum and heart are predilection sites for AApoAII amyloid deposition in CD-1 Swiss mice used for toxicity studies. Pulmonary amyloid indicates AApoAII

Abstract

Amyloid deposits represent frequent histological findings in SPF strains of mice mainly used for toxicological studies. Usually, these are deposits of reactive amyloid (AA-amyloid) derived from the acute phase protein serum amyloid A (SAA). The SAA is an apoprotein of high density lipoprotein (apoSAA). Senescence-accelerated amyloid (ASsam) occurs in a special strain of mice. This type of amyloid is derived from apolipoprotein-AII and, therefore, is called AApoAII. Recently, C57B1/Ka control mice not treated for long duration with immunosuppressive agents, were found to have developed AApoAII-amyloidosis with a predilection for the deposits in the ileum (HogenEsch et al. 1993). In the present study, SPF CD-1 Swiss outbred mice, used for chronic toxicity experiments, were investigated. Amyloidosis was diagnosed by haematoxylin and eosin staining. The tissue localization of amyloid was recorded and confirmed by Congo red staining. The chemical type of amyloid was investigated by peroxidase antiperoxidase (PAP)-immunostaining using anti-murine AA and anti-murine AApoAII antibodies. Those animals which died during the study and the mice killed at end of the experiment, aged 18 months, from treated as well as non-treated control groups, showed AApoAII-amyloid deposits with similar prevalence. The AApoAII amyloid had organ predilection for gut, heart and lung tissue. A group of animals was euthanazed intercurrently at a young age, since they suffered from spontaneous dermatitis associated with Staphylococcus aureus infection. Sixty-eight percent had reactive amyloid deposits found primarily in spleen, liver, kidney and gut. From these findings and literature data on various other mouse strains, it is concluded that in mice used for toxicity studies, AA and AApoAII types of amyloidosis may be expected. The deposition patterns of these types of amyloid are slightly different. AA-amyloid has a predilection for spleen, liver, gut and kidney, and is often associated with inflammatory lesions of the skin, whereas masses of amyloid in lung, heart and ileum suggest AApoAII. Pulmonary amyloid appears to represent the most reliable deposition criterion for discriminating between both types of amyloidosis.