Transgenic mouse model of AA amyloidosis

Alan Solomon, Deborah T. Weiss, Maria Schell, Rudi Hrncic, Charles L. Murphy, Jonathan Wall, M. Donald McGavin, Hong Jun Pan, George Kabalka, Michael J. Paulus

Research output: Contribution to journalArticle

58 Citations (Scopus)

Abstract

AA amyloidosis can be induced in mice experimentally through injection of certain chemical or biological compounds. However, the usefulness of this approach is limited by its dependence on exogenous inflammatory agents that stimulate cytokines to increase the synthesis of precursor serum amyloid A (SAA) protein and the transitory nature of the pathological fibrillar deposits. We now report that transgenic mice carrying the human interleukin 6 gene under the control of the metallothionein-I promoter had markedly increased concentrations of SAA and developed amyloid in the spleen, liver, and kidneys by 3 months of age. At the time of death about 6 months later, organs obtained from these animals had extensive amyloid deposits. This disease process was apparent radiographically using small-animal computer axial tomography and magnetic resonance imaging equipment. The AA nature of the amyloid was evidenced immunohistochemically and was unequivocally established by sequence analysis of protein extracted from the fibrils. The availability of this unique in vivo experimental model of AA amyloidosis provides the means to assess the therapeutic efficacy of agents designed to reduce or prevent the fibrillar deposits found in AA and other types of amyloid-associated disease.

Original languageEnglish (US)
Pages (from-to)1267-1272
Number of pages6
JournalAmerican Journal of Pathology
Volume154
Issue number4
DOIs
StatePublished - Jan 1 1999

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Amyloidosis
Amyloid
Transgenic Mice
Serum Amyloid A Protein
Animal Structures
Metallothionein
Protein Sequence Analysis
Amyloid Plaques
Interleukin-6
Theoretical Models
Spleen
Tomography
Magnetic Resonance Imaging
Cytokines
Kidney
Equipment and Supplies
Injections
Liver
Genes
Therapeutics

All Science Journal Classification (ASJC) codes

  • Pathology and Forensic Medicine

Cite this

Solomon, A., Weiss, D. T., Schell, M., Hrncic, R., Murphy, C. L., Wall, J., ... Paulus, M. J. (1999). Transgenic mouse model of AA amyloidosis. American Journal of Pathology, 154(4), 1267-1272. https://doi.org/10.1016/S0002-9440(10)65378-3

Transgenic mouse model of AA amyloidosis. / Solomon, Alan; Weiss, Deborah T.; Schell, Maria; Hrncic, Rudi; Murphy, Charles L.; Wall, Jonathan; McGavin, M. Donald; Pan, Hong Jun; Kabalka, George; Paulus, Michael J.

In: American Journal of Pathology, Vol. 154, No. 4, 01.01.1999, p. 1267-1272.

Research output: Contribution to journalArticle

Solomon, A, Weiss, DT, Schell, M, Hrncic, R, Murphy, CL, Wall, J, McGavin, MD, Pan, HJ, Kabalka, G & Paulus, MJ 1999, 'Transgenic mouse model of AA amyloidosis', American Journal of Pathology, vol. 154, no. 4, pp. 1267-1272. https://doi.org/10.1016/S0002-9440(10)65378-3
Solomon, Alan ; Weiss, Deborah T. ; Schell, Maria ; Hrncic, Rudi ; Murphy, Charles L. ; Wall, Jonathan ; McGavin, M. Donald ; Pan, Hong Jun ; Kabalka, George ; Paulus, Michael J. / Transgenic mouse model of AA amyloidosis. In: American Journal of Pathology. 1999 ; Vol. 154, No. 4. pp. 1267-1272.
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