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.
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.
Authors: S T Waters; S M Fu; F Gaskin; U S Deshmukh; S S Sung; C C Kannapell; K S Tung; S B McEwen; M McDuffie Journal: Clin Immunol Date: 2001-09 Impact factor: 3.969
Authors: Matlock A Jeffries; Mikhail Dozmorov; Yuhong Tang; Joan T Merrill; Jonathan D Wren; Amr H Sawalha Journal: Epigenetics Date: 2011-05-01 Impact factor: 4.528
Authors: Geert J De Vries; Emilie F Rissman; Richard B Simerly; Liang-Yo Yang; Elka M Scordalakes; Catherine J Auger; Amanda Swain; Robin Lovell-Badge; Paul S Burgoyne; Arthur P Arnold Journal: J Neurosci Date: 2002-10-15 Impact factor: 6.167
Authors: Yuichiro Itoh; Lisa C Golden; Noriko Itoh; Macy Akiyo Matsukawa; Emily Ren; Vincent Tse; Arthur P Arnold; Rhonda R Voskuhl Journal: J Clin Invest Date: 2019-08-12 Impact factor: 14.808
Authors: Xuqi Chen; Lixin Wang; Dawn H Loh; Christopher S Colwell; Yvette Taché; Karen Reue; Arthur P Arnold Journal: Horm Behav Date: 2015-07-29 Impact factor: 3.587