Quantitative high-resolution microradiographic imaging of amyloid deposits in a novel murine model of AA amyloidosis

Jonathan Wall, Stephen Kennel, Michael J. Paulus, Shaun Gleason, Jens Gregor, Justin Baba, Maria Schell, Tina Richey, Brian O'Nuallain, Robert Donnell, Philip N. Hawkins, Deborah T. Weiss, Alan Solomon

Research output: Contribution to journalArticle

22 Citations (Scopus)

Abstract

The mouse model of experimentally induced systemic AA amyloidosis is long established, well validated, and closely analogous to the human form of this disease. However, the induction of amyloid by experimental inflammation is unpredictable, inconsistent, and difficult to modulate. We have previously shown that murine AA amyloid deposits can be imaged using iodine-123 labeled SAP scintigraphy and report here substantial refinements in both the imaging technology and the mouse model itself. In this regard, we have generated a novel prototype of AA amyloid in which mice expressing the human interleukin 6 gene, when given amyloid enhancing factor, develop extensive and progressive systemic AA deposition without an inflammatory stimulus, i.e., a transgenic rapidly inducible amyloid disease (TRIAD) mouse. Additionally, we have constructed high-resolution micro single photon emission computed tomography (SPECT)/computed tomography (CT) instrumentation that provides images revealing the precise anatomic location of amyloid deposits labeled by radioiodinated serum amyloid P component (SAP). Based on reconstructed microSPECT/CT images, as well as autoradiographic, isotope biodistribution, and quantitative histochemical analyses, the 125I-labeled SAP tracer bound specifically to hepatic and splenic amyloid in the TRIAD animals. The ability to discern radiographically the extent of amyloid burden in the TRIAD model provides a unique opportunity to evaluate the therapeutic efficacy of pharmacologic compounds designed to inhibit fibril formation or effect amyloid resolution.

Original languageEnglish (US)
Pages (from-to)149-156
Number of pages8
JournalAmyloid
Volume12
Issue number3
DOIs
StatePublished - Sep 1 2005

Fingerprint

Amyloid Plaques
Amyloidosis
Amyloid
Serum Amyloid P-Component
Animal Diseases
Isotopes
Radionuclide Imaging
Iodine
Interleukin-6
Tomography
Inflammation
Technology
Liver
Genes

All Science Journal Classification (ASJC) codes

  • Internal Medicine

Cite this

Quantitative high-resolution microradiographic imaging of amyloid deposits in a novel murine model of AA amyloidosis. / Wall, Jonathan; Kennel, Stephen; Paulus, Michael J.; Gleason, Shaun; Gregor, Jens; Baba, Justin; Schell, Maria; Richey, Tina; O'Nuallain, Brian; Donnell, Robert; Hawkins, Philip N.; Weiss, Deborah T.; Solomon, Alan.

In: Amyloid, Vol. 12, No. 3, 01.09.2005, p. 149-156.

Research output: Contribution to journalArticle

Wall, J, Kennel, S, Paulus, MJ, Gleason, S, Gregor, J, Baba, J, Schell, M, Richey, T, O'Nuallain, B, Donnell, R, Hawkins, PN, Weiss, DT & Solomon, A 2005, 'Quantitative high-resolution microradiographic imaging of amyloid deposits in a novel murine model of AA amyloidosis', Amyloid, vol. 12, no. 3, pp. 149-156. https://doi.org/10.1080/13506120500222359
Wall, Jonathan ; Kennel, Stephen ; Paulus, Michael J. ; Gleason, Shaun ; Gregor, Jens ; Baba, Justin ; Schell, Maria ; Richey, Tina ; O'Nuallain, Brian ; Donnell, Robert ; Hawkins, Philip N. ; Weiss, Deborah T. ; Solomon, Alan. / Quantitative high-resolution microradiographic imaging of amyloid deposits in a novel murine model of AA amyloidosis. In: Amyloid. 2005 ; Vol. 12, No. 3. pp. 149-156.
@article{ef8a60c3aecd481ba7c9b1eab69636e9,
title = "Quantitative high-resolution microradiographic imaging of amyloid deposits in a novel murine model of AA amyloidosis",
abstract = "The mouse model of experimentally induced systemic AA amyloidosis is long established, well validated, and closely analogous to the human form of this disease. However, the induction of amyloid by experimental inflammation is unpredictable, inconsistent, and difficult to modulate. We have previously shown that murine AA amyloid deposits can be imaged using iodine-123 labeled SAP scintigraphy and report here substantial refinements in both the imaging technology and the mouse model itself. In this regard, we have generated a novel prototype of AA amyloid in which mice expressing the human interleukin 6 gene, when given amyloid enhancing factor, develop extensive and progressive systemic AA deposition without an inflammatory stimulus, i.e., a transgenic rapidly inducible amyloid disease (TRIAD) mouse. Additionally, we have constructed high-resolution micro single photon emission computed tomography (SPECT)/computed tomography (CT) instrumentation that provides images revealing the precise anatomic location of amyloid deposits labeled by radioiodinated serum amyloid P component (SAP). Based on reconstructed microSPECT/CT images, as well as autoradiographic, isotope biodistribution, and quantitative histochemical analyses, the 125I-labeled SAP tracer bound specifically to hepatic and splenic amyloid in the TRIAD animals. The ability to discern radiographically the extent of amyloid burden in the TRIAD model provides a unique opportunity to evaluate the therapeutic efficacy of pharmacologic compounds designed to inhibit fibril formation or effect amyloid resolution.",
author = "Jonathan Wall and Stephen Kennel and Paulus, {Michael J.} and Shaun Gleason and Jens Gregor and Justin Baba and Maria Schell and Tina Richey and Brian O'Nuallain and Robert Donnell and Hawkins, {Philip N.} and Weiss, {Deborah T.} and Alan Solomon",
year = "2005",
month = "9",
day = "1",
doi = "10.1080/13506120500222359",
language = "English (US)",
volume = "12",
pages = "149--156",
journal = "Amyloid : the international journal of experimental and clinical investigation : the official journal of the International Society of Amyloidosis",
issn = "1350-6129",
publisher = "Informa Healthcare",
number = "3",

}

TY - JOUR

T1 - Quantitative high-resolution microradiographic imaging of amyloid deposits in a novel murine model of AA amyloidosis

AU - Wall, Jonathan

AU - Kennel, Stephen

AU - Paulus, Michael J.

AU - Gleason, Shaun

AU - Gregor, Jens

AU - Baba, Justin

AU - Schell, Maria

AU - Richey, Tina

AU - O'Nuallain, Brian

AU - Donnell, Robert

AU - Hawkins, Philip N.

AU - Weiss, Deborah T.

AU - Solomon, Alan

PY - 2005/9/1

Y1 - 2005/9/1

N2 - The mouse model of experimentally induced systemic AA amyloidosis is long established, well validated, and closely analogous to the human form of this disease. However, the induction of amyloid by experimental inflammation is unpredictable, inconsistent, and difficult to modulate. We have previously shown that murine AA amyloid deposits can be imaged using iodine-123 labeled SAP scintigraphy and report here substantial refinements in both the imaging technology and the mouse model itself. In this regard, we have generated a novel prototype of AA amyloid in which mice expressing the human interleukin 6 gene, when given amyloid enhancing factor, develop extensive and progressive systemic AA deposition without an inflammatory stimulus, i.e., a transgenic rapidly inducible amyloid disease (TRIAD) mouse. Additionally, we have constructed high-resolution micro single photon emission computed tomography (SPECT)/computed tomography (CT) instrumentation that provides images revealing the precise anatomic location of amyloid deposits labeled by radioiodinated serum amyloid P component (SAP). Based on reconstructed microSPECT/CT images, as well as autoradiographic, isotope biodistribution, and quantitative histochemical analyses, the 125I-labeled SAP tracer bound specifically to hepatic and splenic amyloid in the TRIAD animals. The ability to discern radiographically the extent of amyloid burden in the TRIAD model provides a unique opportunity to evaluate the therapeutic efficacy of pharmacologic compounds designed to inhibit fibril formation or effect amyloid resolution.

AB - The mouse model of experimentally induced systemic AA amyloidosis is long established, well validated, and closely analogous to the human form of this disease. However, the induction of amyloid by experimental inflammation is unpredictable, inconsistent, and difficult to modulate. We have previously shown that murine AA amyloid deposits can be imaged using iodine-123 labeled SAP scintigraphy and report here substantial refinements in both the imaging technology and the mouse model itself. In this regard, we have generated a novel prototype of AA amyloid in which mice expressing the human interleukin 6 gene, when given amyloid enhancing factor, develop extensive and progressive systemic AA deposition without an inflammatory stimulus, i.e., a transgenic rapidly inducible amyloid disease (TRIAD) mouse. Additionally, we have constructed high-resolution micro single photon emission computed tomography (SPECT)/computed tomography (CT) instrumentation that provides images revealing the precise anatomic location of amyloid deposits labeled by radioiodinated serum amyloid P component (SAP). Based on reconstructed microSPECT/CT images, as well as autoradiographic, isotope biodistribution, and quantitative histochemical analyses, the 125I-labeled SAP tracer bound specifically to hepatic and splenic amyloid in the TRIAD animals. The ability to discern radiographically the extent of amyloid burden in the TRIAD model provides a unique opportunity to evaluate the therapeutic efficacy of pharmacologic compounds designed to inhibit fibril formation or effect amyloid resolution.

UR - http://www.scopus.com/inward/record.url?scp=27144437903&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=27144437903&partnerID=8YFLogxK

U2 - 10.1080/13506120500222359

DO - 10.1080/13506120500222359

M3 - Article

C2 - 16194869

AN - SCOPUS:27144437903

VL - 12

SP - 149

EP - 156

JO - Amyloid : the international journal of experimental and clinical investigation : the official journal of the International Society of Amyloidosis

JF - Amyloid : the international journal of experimental and clinical investigation : the official journal of the International Society of Amyloidosis

SN - 1350-6129

IS - 3

ER -