Quantitative tomography of early-onset spontaneous AA amyloidosis in interleukin 6 transgenic mice

Jonathan Wall, Tina Richey, Amy Allen, Robert Donnell, Stephen Kennel, Alan Solomon

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15 Citations (Scopus)

Abstract

Mice that constitutively express the human interleukin 6 (huIL6) protein from a heritable transgene (H2-L d-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-L d-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.

Original languageEnglish (US)
Pages (from-to)542-550
Number of pages9
JournalComparative Medicine
Volume58
Issue number6
StatePublished - Dec 1 2008

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amyloidosis
tomography
Amyloidosis
amyloid
Amyloid
interleukin-6
Transgenic Mice
Tomography
Interleukin-6
genetically modified organisms
mice
Amyloid Plaques
Deposits
Liver
Serum Amyloid A Protein
Apoproteins
Acute-Phase Proteins
Single photon emission computed tomography
Diagnostic Imaging
HDL Lipoproteins

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)
  • veterinary(all)

Cite this

Quantitative tomography of early-onset spontaneous AA amyloidosis in interleukin 6 transgenic mice. / Wall, Jonathan; Richey, Tina; Allen, Amy; Donnell, Robert; Kennel, Stephen; Solomon, Alan.

In: Comparative Medicine, Vol. 58, No. 6, 01.12.2008, p. 542-550.

Research output: Contribution to journalArticle

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