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Updated: Jun 14, 2026
12:04
The bm12 Inducible Model of Systemic Lupus Erythematosus (SLE) in C57BL/6 Mice
Published on: November 1, 2015
Female mice with a Xist deletion in B cells can develop lupus-associated phenotypes
Claudia D Lovell1, Nikhil Jiwrajka2, Natalie E Toothacre1
1Department of Biomedical Science, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
Cell Reports
|June 12, 2026
Summary
Impaired X chromosome inactivation (XCI) in B cells contributes to systemic lupus erythematosus (SLE) in females. Female mice with B cell-specific Xist deletion developed SLE-like symptoms, indicating a direct link.
Area of Science:
- Immunology
- Genetics
- Autoimmune Diseases
Background:
- Systemic lupus erythematosus (SLE) is a female-predominant autoimmune disease.
- X chromosome inactivation (XCI) equalizes X-linked gene expression in XX females.
- Aberrant X-linked gene expression and Xist RNA mislocalization in SLE B cells suggest impaired XCI.
Purpose of the Study:
- To investigate the role of impaired XCI in B cells in the development of SLE.
- To determine if B cell-specific Xist deletion leads to SLE phenotypes.
Main Methods:
- Generated female mice with a B cell-specific deletion of Xist (Xist cKO).
- Administered pristane to Xist cKO mice to induce SLE phenotypes.
- Analyzed B cell subsets, autoantibody production, and gene expression in Xist cKO mice.
Main Results:
- Xist cKO mice spontaneously developed SLE phenotypes, including expanded activated B cells, autoantibodies, and glomerulonephritis.
- Pristane treatment exacerbated SLE phenotypes in Xist cKO mice, increasing anti-dsDNA autoantibodies.
- Activated B cells in Xist cKO mice showed increased X-linked/autosomal gene expression and H3K27me3 depletion.
Conclusions:
- Impaired XCI maintenance in B cells directly contributes to SLE pathogenesis.
- This impairment leads to female-biased SLE-associated phenotypes.
- Xist deficiency in B cells dysregulates immune responses, promoting autoimmunity.
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01:58X-Inactivation
The human X chromosome contains over ten times the number of genes as in the Y chromosome. Since males have only one X chromosome, and females have two, one might expect females to produce twice as many of the proteins, with undesirable results.
01:19X-linked Traits
In most mammalian species, females have two X sex chromosomes and males have an X and Y. As a result, mutations on the X chromosome in females may be masked by the presence of a normal allele on the second X. In contrast, a mutation on the X chromosome in males more often causes observable biological defects, as there is no normal X to compensate. Trait variations arising from mutations on the X chromosome are called “X-linked”.
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