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PMID: 1361492 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Beta cell expression of endogenous xenotropic retrovirus distinguishes diabetes-susceptible NOD/Lt from resistant NON/Lt mice.

The Journal of clinical investigation ·Vol. 90 ·No. 6 ·1992-12-00 ·Pages 2220-7

Gaskins HR, Prochazka M, Hamaguchi K, Serreze DV, Leiter EH

Abstract

Endogeneous retroviral expression in beta cells is a feature of prediabetes in nonobese diabetic (NOD) mice. The purpose of this study was to characterize the class-specific pattern of retroviral gene expression in NOD/Lt beta cells versus a related, but diabetes-resistant strain, NON/Lt. Electron microscopic comparison of beta cells from both strains indicated low constitutive expression of the intracisternal type A (IAP) retroviral class. However, NOD beta cells, in contrast to NON beta cells, expressed an additional intracisternal retroviral form resembling a type C particle. Antibodies against both IAP and type C were detected in NOD, with the humoral response to type C, but not IAP, preceding decline in beta cell function. RNA was extracted from freshly isolated islets from NOD and NON males. Comparative Northern blot analysis of total type C retroviral gene expression using a gag-pol DNA probe corroborated expression of endogenous type C proviruses in both NOD and NON islet cells and thymus. Use of class-specific retroviral probes identified the class of expressed endogenous retrovirus distinguishing the two inbred strains. The single ecotropic provirus present in both the NOD and NON genome (Emv-30) was not expressed in islets or thymus of either strain. Comparison of endogenous xenotropic provirus content by Southern blot analysis revealed two unique xenotropic loci (Xmv-65, -66) in NOD; 8.4 and 3.0 kb xenotropic envelope (env) RNA transcripts were detected in NOD, but not NON islets and thymus. NON contained three xenotropic loci common to other inbred strains (Xmv-21, -25, and -28). Both strains were partially characterized for content of recombinant (polytropic and modified polytropic) proviruses. IAP RNA expression was common to both NOD and NON islets and hence could not be specifically associated with the unique intracisternal type C particle found in NOD, but not NON beta cells. In conclusion, this study shows that expression of xenotropic type C but not IAP distinguishes retroviral activity in NOD/Lt versus NON/Lt beta cells. The potential pathogenic role of retroviral gene expression in NOD beta cells is discussed.

Related Genes
Xmv-65 Xmv-66
MeSH Terms
Animals Antibodies, Viral/immunology Blotting, Northern DNA, Viral/analysis Diabetes Mellitus, Type 1/microbiology Female Gene Expression Genes, Viral Islets of Langerhans/microbiology Male Mice Mice, Inbred NOD/microbiology Microscopy, Electron Polymorphism, Restriction Fragment Length Proviruses/genetics,growth & development Retroviridae/growth & development,immunology,ultrastructure Viral Structural Proteins/genetics
Chemicals
Antibodies, Viral DNA, Viral Viral Structural Proteins
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Gaskins H R
Jackson Laboratory, Bar Harbor, Maine 04609.
Prochazka M
Hamaguchi K
Serreze D V
Leiter E H
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Article Info
Journal
The Journal of clinical investigation
Abbr.
J Clin Invest
ISSN
0021-9738
DOI
10.1172/JCI116107
Published
1992-12-00
Pages
2220-7
Language
English
Region
United States
NLM ID
7802877
PMCID
PMC443372
Subset
IM
Grants
NIDDK NIH HHS · DK 27722 · United States
NIDDK NIH HHS · DK 36175 · United States
External Links
PubMed source DOI: 10.1172/JCI116107 PMC Full Text View journal details
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