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PMID: 1279667 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Insulitis in transgenic mice expressing tumor necrosis factor beta (lymphotoxin) in the pancreas.

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 89 ·No. 21 ·1992-11-01 ·Pages 10036-40

Picarella DE, Kratz A, Li CB, Ruddle NH, Flavell RA

Abstract

Tumor necrosis factor beta (TNF-beta) (lymphotoxin) may play an important role in the immune response and pathologic inflammatory diseases. Insulitis is an important early step in the development of insulin-dependent diabetes mellitus. To understand better the role of TNF-beta in the regulation of inflammation and type 1 diabetes, we produced transgenic mice in which the murine TNF-beta gene was regulated by the rat insulin II promoter. The transgene was expressed in the pancreas, kidney, and skin of transgenic mice. The expression of TNF-beta in the pancreas of transgenic mice resulted in a leukocytic inflammatory infiltrate consisting primarily of B220+ IgM+ B cells and CD4+ and CD8+ T cells. The insulitis is reminiscent of the early stages of diabetes, though the mice did not progress to diabetes.

MeSH Terms

Animals Blotting, Northern Insulin/biosynthesis Islets of Langerhans/metabolism,pathology Lymphotoxin-alpha/biosynthesis,genetics Mice Mice, Transgenic Pancreas/metabolism,pathology Pancreatic Diseases/genetics,pathology RNA/genetics,isolation & purification RNA, Messenger/genetics,isolation & purification,metabolism Rats Restriction Mapping

Chemicals

Insulin Lymphotoxin-alpha RNA, Messenger RNA

Authors & Affiliations

5 authors, click to expand affiliations / ORCID

Picarella D E

Section of Immunobiology, Yale University School of Medicine, New Haven, CT 06510.

Kratz A

Li C B

Ruddle N H

Flavell R A

References (21)

21 references, click to expand

Helper T-cell subsets: phenotype, function and the role of lymphokines in regulating their development.
Immunol Rev. 1991 Oct;123:115-44 PMID: 1684776
Synapsin I (protein I), a nerve terminal-specific phosphoprotein. I. Its general distribution in synapses of the central and peripheral nervous system demonstrated by immunofluorescence in frozen and plastic sections.
J Cell Biol. 1983 May;96(5):1337-54 PMID: 6404910
Exclusive expression of MHC class II proteins on CD45+ cells in pancreatic islets of NOD mice.
Diabetes. 1991 May;40(5):648-51 PMID: 1827081
Identification and mapping to chromosome 1 of a susceptibility locus for periinsulitis in non-obese diabetic mice.
Nature. 1991 Sep 19;353(6341):260-2 PMID: 1896073
Loss of pancreatic islet tolerance induced by beta-cell expression of interferon-gamma.
Nature. 1990 Aug 30;346(6287):844-7 PMID: 2118234
Insulin-dependent diabetes mellitus induced in transgenic mice by ectopic expression of class II MHC and interferon-gamma.
Cell. 1988 Mar 11;52(5):773-82 PMID: 2449974
Cyclophosphamide-induced diabetes in NOD/WEHI mice. Evidence for suppression in spontaneous autoimmune diabetes mellitus.
Diabetes. 1989 Apr;38(4):441-7 PMID: 2522407
Comparison of high- and low-diabetes-incidence NOD mouse strains.
Diabetes. 1989 Oct;38(10):1296-300 PMID: 2529158
Diabetes and tolerance in transgenic mice expressing class II MHC molecules in pancreatic beta cells.
Cell. 1988 Apr 8;53(1):159-68 PMID: 2964908
HLA class II induction in human islet cells by interferon-gamma plus tumour necrosis factor or lymphotoxin.
Nature. 1987 Mar 19-25;326(6110):304-6 PMID: 3102976
The murine tumor necrosis factor-beta (lymphotoxin) gene sequence.
Nucleic Acids Res. 1987 May 11;15(9):3937 PMID: 3588316
Nucleotide sequence of the murine TNF locus, including the TNF-alpha (tumor necrosis factor) and TNF-beta (lymphotoxin) genes.
Nucleic Acids Res. 1987 Nov 11;15(21):9083-4 PMID: 3684584
Genetic analysis of autoimmune type 1 diabetes mellitus in mice.
Nature. 1991 Jun 13;351(6327):542-7 PMID: 1675432
NOR/Lt mice: MHC-matched diabetes-resistant control strain for NOD mice.
Diabetes. 1992 Jan;41(1):98-106 PMID: 1727742
Type 1 diabetes in mice is linked to the interleukin-1 receptor and Lsh/Ity/Bcg genes on chromosome 1.
Nature. 1991 Sep 19;353(6341):262-5 PMID: 1832743
An antibody to lymphotoxin and tumor necrosis factor prevents transfer of experimental allergic encephalomyelitis.
J Exp Med. 1990 Oct 1;172(4):1193-200 PMID: 2212948
Three distinct classes of regulatory cytokines control endothelial cell MHC antigen expression. Interactions with immune gamma interferon differentiate the effects of tumor necrosis factor and lymphotoxin from those of leukocyte alpha and fibroblast beta interferons.
J Exp Med. 1988 Mar 1;167(3):794-804 PMID: 2450953
Cloning and expression of murine lymphotoxin cDNA.
J Immunol. 1987 Jun 15;138(12):4496-501 PMID: 2884262
Overlapping patterns of activation of human endothelial cells by interleukin 1, tumor necrosis factor, and immune interferon.
J Immunol. 1986 Sep 15;137(6):1893-6 PMID: 3091693
A high proportion of T lymphocytes that infiltrate H-2-incompatible heart allografts in vivo express genes encoding cytotoxic cell-specific serine proteases, but do not express the MEL-14-defined lymph node homing receptor.
J Exp Med. 1988 Mar 1;167(3):1124-36 PMID: 3280725
Monocyte function in IDDM patients and healthy individuals.
Scand J Immunol. 1990 Sep;32(3):297-311 PMID: 1698309

Article Info

Journal

Proceedings of the National Academy of Sciences of the United States of America

Abbr.

Proc Natl Acad Sci U S A

ISSN

0027-8424

DOI

10.1073/pnas.89.21.10036

Published

1992-11-01

Pages

10036-40

Language

English

Region

United States

NLM ID

7505876

PMCID

PMC50272

Subset

Grants

NIAID NIH HHS · AI 07019 · United States

NIDDK NIH HHS · P01 DK 43078 · United States

NCI NIH HHS · R01 CA 47878 · United States

External Links

PubMed source DOI: 10.1073/pnas.89.21.10036 PMC Full Text View journal details

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Insulitis in transgenic mice expressing tumor necrosis factor beta (lymphotoxin) in the pancreas.

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