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Open Access Quantitative Tomography of Early-Onset Spontaneous AA Amyloidosis in Interleukin 6 Transgenic Mice

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Abstract:

Mice that constitutively express the human interleukin 6 (huIL6) protein from a heritable transgene (H2-Ld-IL-6) express high levels of the acute-phase reactant, serum amyloid protein A, a liver-derived apoprotein of high-density lipoprotein that is the precursor of AA amyloid. Typically at approximately 5 mo of age B6(C)-Tg(H2-Ld-IL-6)Kish (H2/huIL-6) animals begin to develop splenic deposits of AA amyloid, which progress to involve the liver, kidney, and vasculature, ultimately resulting in death due to severe systemic AA amyloidosis at 8 to 9 mo of age. These mice provide a robust model in which to study novel therapeutic and diagnostic imaging agents for AA amyloidosis. We recently have noted a change in onset of spontaneous disease, as evidenced by 2 female transgenic mice that were found moribund at only 5 mo of age. Extensive hepatosplenic amyloid deposits in both mice were identified and quantified by single-photon emission computed tomography, which further revealed heterogeneous distribution of radiotracer in the spleen indicating a distinction between amyloid-laden red pulp and the disease-free lymphoid follicles. The AA nature of the deposits was evidenced immunohistochemically and by mass spectrometric analyses of extracted amyloid fibrils. Our studies have documented the manifestation of early-onset, severe, spontaneous AA amyloidosis in 2- to 5-mo-old H2/huIL-6 mice; we hypothesize that this disease is due to genetic rather than environmental factors.

Document Type: Research Article

Affiliations: 1: Human Immunology and Cancer Program, Graduate School of Medicine, University of Tennessee, Knoxville, TN 2: Department of Pathobiology, College of Veterinary Medicine, University of Tennessee, Knoxville, TN

Publication date: December 1, 2008

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  • Comparative Medicine (CM), an international journal of comparative and experimental medicine, is the leading English-language publication in the field and is ranked by the Science Citation Index in the upper third of all scientific journals. The mission of CM is to disseminate high-quality, peer-reviewed information that expands biomedical knowledge and promotes human and animal health through the study of laboratory animal disease, animal models of disease, and basic biologic mechanisms related to disease in people and animals.

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