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Updated: Aug 12, 2026
The bm12 Inducible Model of Systemic Lupus Erythematosus (SLE) in C57BL/6 Mice
Published on: November 1, 2015
Association of murine lupus and thymic full-length endogenous retroviral expression maps to a bone marrow stem cell
A M Krieg1, M F Gourley, A D Steinberg
1Cellular Immunology Section, ARB, NIAMS, National Institutes of Health, Bethesda, MD 20892.
Abstract:
Recent studies of thymic gene expression in murine lupus have demonstrated 8.4-kb (full-length size) modified polytropic (Mpmv) endogenous retroviral RNA. In contrast, normal control mouse strains do not produce detectable amounts of such RNA in their thymuses. Prior studies have attributed a defect in experimental tolerance in murine lupus to a bone marrow stem cell rather than to the thymic epithelium; in contrast, infectious retroviral expression has been associated with the thymic epithelium, rather than with the bone marrow stem cell. The present study was designed to determine whether the abnormal Mpmv expression associated with murine lupus mapped to thymic epithelium or to a marrow precursor. Lethally irradiated control and lupus-prone mice were reconstituted with T cell depleted bone marrow; one month later their thymuses were studied for endogenous retroviral RNA and protein expression. Recipients of bone marrow from nonautoimmune donors expressed neither 8.4-kb Mpmv RNA nor surface MCF gp70 in their thymuses. In contrast, recipients of bone marrow from autoimmune NZB or BXSB donors expressed thymic 8.4-kb Mpmv RNA and mink cell focus-forming gp70. These studies demonstrate that lupus-associated 8.4-kb Mpmv endogenous retroviral expression is determined by bone marrow stem cells.
Insights
Murine lupus exhibits abnormal thymic gene expression of modified polytropic (Mpmv) endogenous retroviral RNA. These studies reveal this Mpmv expression originates from bone marrow stem cells, not thymic epithelium.
Area of Science:
- Immunology
- Virology
- Genetics
Background:
- Murine lupus models show abnormal 8.4-kilobase (kb) modified polytropic (Mpmv) endogenous retroviral RNA in thymic gene expression.
- Normal mice do not produce detectable levels of this Mpmv RNA in their thymuses.
- Previous research debated whether lupus-related tolerance defects stem from bone marrow stem cells or thymic epithelium.
Purpose of the Study:
- To determine if abnormal Mpmv expression in murine lupus is linked to thymic epithelium or bone marrow precursors.
- To investigate the cellular origin of endogenous retroviral RNA associated with autoimmune disease.
Main Methods:
- Lethally irradiated control and lupus-prone mice were reconstituted with T cell-depleted bone marrow.
- Thymuses were analyzed for endogenous retroviral RNA and protein expression one month post-transplantation.
- Recipient mice received bone marrow from either nonautoimmune or autoimmune (NZB/BXSB) donors.
Main Results:
- Recipients of bone marrow from nonautoimmune donors showed no 8.4-kb Mpmv RNA or surface MCF gp70 in their thymuses.
- Recipients of bone marrow from autoimmune NZB or BXSB donors exhibited thymic 8.4-kb Mpmv RNA and mink cell focus-forming gp70.
- These findings indicate a bone marrow stem cell-dependent origin for Mpmv expression.
Conclusions:
- Lupus-associated 8.4-kb Mpmv endogenous retroviral expression is determined by bone marrow stem cells.
- The cellular source of this abnormal retroviral expression in lupus is the hematopoietic stem cell population.
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