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Updated: May 22, 2026

A Non-random Mouse Model for Pharmacological Reactivation of Mecp2 on the Inactive X Chromosome
Published on: May 22, 2019
The XX sex chromosome complement in mice is associated with increased spontaneous lupus compared with XY
Manda V Sasidhar1, Noriko Itoh, Stefan M Gold
1Department of Neurology, David Geffen School of Medicine, University of California, Los Angeles, California 90095, USA.
Objectives:
Many autoimmune diseases are characterised by a female predominance. This may be caused by sex hormones, sex chromosomes or both. This report uses a transgenic mouse model to investigate how sex chromosome complement, not confounded by differences in gonadal type, might contribute to lupus pathogenesis.
Methods:
Transgenic NZM2328 mice were created by deletion of the Sry gene from the Y chromosome, thereby separating genetic from gonadal sex. Survival, renal histopathology and markers of immune activation were compared in mice carrying the XX versus the XY(-) sex chromosome complement, with each genotype being ovary bearing.
Results:
Mice with XX sex chromosome complement compared with XY(-) exhibited poorer survival rates and increased kidney pathology. Splenic T lymphocytes from XX mice demonstrated upregulated X-linked CD40 ligand expression and higher levels of activation markers ex vivo. Increased MMP, TGF and IL-13 production was found, while IL-2 was lower in XX mice. An accumulation of splenic follicular B cells and peritoneal marginal zone B cells was observed, coupled with upregulated costimulatory marker expression on B cells in XX mice.
Conclusion:
These data show that the XX sex chromosome complement, compared with XY(-), is associated with accelerated spontaneous lupus.
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