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

Comp Med. 2008 Dec;58(6):542-50.


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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Age Factors
  • Amino Acid Sequence
  • Amyloidosis / diagnostic imaging
  • Amyloidosis / etiology*
  • Amyloidosis / genetics
  • Animals
  • Disease Models, Animal
  • Female
  • Humans
  • Interleukin-6 / genetics*
  • Male
  • Mass Spectrometry
  • Mice
  • Mice, Transgenic
  • Peptide Fragments / genetics
  • Peptide Fragments / metabolism
  • Recombinant Proteins / genetics
  • Serum Amyloid A Protein / genetics
  • Serum Amyloid A Protein / metabolism
  • Tomography, Emission-Computed, Single-Photon
  • Tomography, X-Ray Computed


  • IL6 protein, human
  • Interleukin-6
  • Peptide Fragments
  • Recombinant Proteins
  • Serum Amyloid A Protein