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The bm12 Inducible Model of Systemic Lupus Erythematosus SLE in C57BL/6 Mice
Published on: November 1, 2015
Analysis of thymic endogenous retroviral expression in murine lupus. Genetic and immune studies
1Cellular Immunology Section, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, Maryland 20892.
Abstract:
Inbred mouse genomes contain two subclasses of proviruses related to mink cell focus-forming (MCF) retroviruses: polytropic (Pmv), and modified polytropic (Mpmv). To determine whether one of these subclasses is associated with murine lupus, oligonucleotide probes specific for Pmv or Mpmv sequences were used in Northern analyses. Thymus 8.4 kb Mpmv RNA was expressed in five of five lupus-prone strains and crosses and this expression was not affected by genes that retard or accelerate development of lupus. Two of four leukemia-prone strains expressed low levels of such thymic transcripts, but none of 11 control strains did. 8.4 kb Mpmv RNA expression was not induced in thymuses of control mice by the lpr/lpr or gld/gld genotypes (which cause polyclonal immune activation) nor by treatment with mitogens. In contrast to Mpmv, thymic 8.4 kb Pmv expression was poorly associated with autoimmunity: it was easily detected in nearly all strains, and was increased by polyclonal activation in control mice. These studies indicate that the organ-specific thymic 8.4 kb Mpmv expression (a) is characteristic of several genetic backgrounds which predispose to murine lupus, (b) precedes and does not correlate with disease development, (c) is not due to polyclonal activation, and (d) is regulated independently of 8.4 kb Pmv expression.
Insights
Modified polytropic (Mpmv) retroviral RNA expression in the thymus is linked to murine lupus development. This specific Mpmv RNA expression is characteristic of lupus-prone mice and precedes disease onset.
Area of Science:
- Immunology
- Virology
- Genetics
Background:
- Murine lupus is a complex autoimmune disease.
- Mouse genomes contain two proviral subclasses related to mink cell focus-forming (MCF) retroviruses: polytropic (Pmv) and modified polytropic (Mpmv).
Purpose of the Study:
- To investigate the association between Mpmv or Pmv retroviral subclasses and the development of murine lupus.
- To determine the expression patterns of Mpmv and Pmv in different mouse strains and their correlation with autoimmune conditions.
Main Methods:
- Oligonucleotide probes specific for Pmv or Mpmv sequences were utilized.
- Northern blot analyses were performed on thymus tissues from various mouse strains.
- Expression levels of Mpmv and Pmv RNA were quantified and correlated with disease phenotypes.
Main Results:
- Thymic 8.4 kb Mpmv RNA was consistently expressed in lupus-prone strains, irrespective of genes influencing disease progression.
- Low levels of thymic Mpmv RNA were detected in some leukemia-prone strains, but not in control strains.
- 8.4 kb Mpmv RNA expression was not induced by autoimmune-triggering genotypes (lpr/lpr, gld/gld) or mitogens in control mice, indicating it's not due to polyclonal activation.
- Thymic 8.4 kb Pmv expression showed poor association with autoimmunity, was common across strains, and increased with polyclonal activation in control mice.
Conclusions:
- Organ-specific thymic 8.4 kb Mpmv expression is a characteristic of genetic backgrounds predisposing to murine lupus.
- Mpmv expression precedes disease development and is regulated independently of Pmv expression.
- The findings suggest Mpmv expression is a potential biomarker for lupus susceptibility in mice.
