Incidence of Spontaneous Neoplastic and Nonneoplastic Lesions in Charles River CD-1® Mice Varies with Breeding Origin

Engelhardt, Jeffery A.; Gries, Christian L.; Long, Gerald G.

doi:10.1177/019262339302100603

Cited by 35 publications

(24 citation statements)

References 6 publications

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“…Thus, it appeared not to be related to the treatments used in the experimental groups. This finding confirms other descriptions of amyloidosis in aged CD-1 mice (Conner et al 1983, Frith & Chandra 1991, Engelhardt et al 1993.…”

Section: Discussionsupporting

confidence: 92%

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

1996

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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.

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Section: Discussionsupporting

confidence: 92%

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

1996

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“…Amyloid deposition in multiple sites, including renal glomeruli, has been cited as a common background finding in certain mouse strains including CD1 mice (Engelhardt et al 1993; Frith and Chandra 1991). A search of the NTP databases [Carcinogenesis Bioassay Database System (CBDS; 1971 – 1982) and the Toxicology Data Management System (TDMS; 1982 – present) at http://cebs.niehs.nih.gov], revealed that the most common sites of amyloid deposition in B6C3F1 mice include the kidney, spleen, and liver, with variability in which and how many organs were affected in each mouse (Supplemental Table 1 and Supplemental Table 2).…”

Section: Introductionmentioning

confidence: 99%

Comparison of Renal Amyloid and Hyaline Glomerulopathy in B6C3F1 Mice

et al. 2016

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Due to potential misdiagnosis of hyaline glomerulopathy (HG) for amyloidosis, a retrospective study of B6C3F1 mice from the National Toxicology Program (NTP) archives was undertaken to determine if HG had occurred in prior NTP studies and, if so, if these two glomerular lesions could be routinely discriminated. Kidney slides from 7 amyloid positive control mice, 2 HG positive control mice, 3 normal or negative control mice, and 41 potential HG mice (with renal-only deposits previously diagnosed as amyloid) were evaluated using hematoxylin and eosin, periodic acid Schiff (PAS), Congo red (CR) and Masson’s trichrome (MT) stains. Utilizing these techniques, HG was reliably distinguished from amyloidosis. All 41 potential HG mice had glomerular deposits histochemically inconsistent with amyloid; the deposits were PAS positive and CR negative. Four of the 41 mice were selected for transmission electron microscopy of the glomerular deposits; ultrastructurally the deposits in these animals were consistent with HG and not amyloid. Our findings indicate that HG is a spontaneous lesion in B6C3F1 mice of low occurrence, is commonly misdiagnosed as amyloidosis, and is more likely than amyloid to cause glomerular deposits in mice without evidence of deposits in other tissues. Also, HG can be distinguished from amyloid on H&E evaluation; however, the distinction is improved with use of PAS or CR staining, and/or ultraviolet evaluation.

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“…Hyalinization was not noted in any other organs in this study including the adrenal, which is frequently involved in systemic amyloidosis (Engelhardt, Gries, and Long 1993;Frith and Chandra 1991). A localized gastrointestinal form of amyloidosis that can involve the stomach (AApoAII type) has been described in aged C57BL/Ka mice; however, the incidence of this particular form of amyloidosis was decreased by immunosuppressive therapy that included corticosteroid (HogenEsch et al 1993).…”

Section: Discussionmentioning

confidence: 54%

Hyalinization of the Pyloric Stomach in CD-1 Mice Following Oral (Dietary) Administration of the Corticosteroid Agonists Mometasone Furoate, Budesonide, and Flunisolide

et al. 2011

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The purpose of this study was to compare the toxicity of three marketed corticosteroid receptor agonists (mometasone furoate, budesonide, or flunisolide) to the stomach of female CD-1 mice following oral administration via the diet for up to 52 weeks, with a 16-week recovery period (budesonide and flunisolide). A range of tissues was examined by light microscopy, accompanied by clinical pathology measurements to assess anticipated corticosteroid effects as a surrogate marker of systemic drug exposure. Microscopic changes seen in the stomach with each corticosteroid included pyloric hyalinization. This previously unreported finding was investigated using histochemical and immunohistochemical techniques and was found to consist of hyalinized collagen, in association with increased immunohistochemical signal for transglutaminase-2 and osteopontin. The significance of the osteopontin finding is unclear; however, the ability of transglutaminase-2 to facilitate the formation of degradation resistant protein bonds implies this protein may be involved in the pathogenesis of this change. Furthermore, published evidence that transglutaminase-2 may be induced by a corticosteroid agonist raises the possibility that pyloric stomach hyalinization may be a class effect of corticosteroids via the action of this enzyme.

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Incidence of Spontaneous Neoplastic and Nonneoplastic Lesions in Charles River CD-1® Mice Varies with Breeding Origin

Cited by 35 publications

References 6 publications

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

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

Comparison of Renal Amyloid and Hyaline Glomerulopathy in B6C3F1 Mice

Hyalinization of the Pyloric Stomach in CD-1 Mice Following Oral (Dietary) Administration of the Corticosteroid Agonists Mometasone Furoate, Budesonide, and Flunisolide

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