PubMed 22565825

Referenced in Channelpedia wiki pages of: none

Automatically associated channels: Kir6.2

Title: Female mouse fetal loss mediated by maternal autoantibody.

Authors: Li Wang, Dun Zhou, Ji Lee, Haitao Niu, Thomas W Faust, Stephen Frattini, Czeslawa Kowal, Patricio T Huerta, Bruce T Volpe, Betty Diamond

Journal, date & volume: J. Exp. Med., 2012 Jun 4 , 209, 1083-9

PubMed link:

Systemic lupus erythematosus (SLE), a disease of women during childbearing years, is characterized by the production of double-stranded DNA antibodies. A subset of these antibodies, present in 40% of patients, cross-reacts with the NR2A and NR2B subunits of the N-methyl-d-aspartate receptor (NMDAR). In this study, we show that, in mouse models, these antibodies cause a loss of female fetus viability by inducing apoptosis of NR2A-expressing neurons within the brainstem late in fetal development; gender specificity derives from a time-dependent increased expression of NR2A in female brainstem or increased vulnerability of female fetal neurons to signaling through NR2A-containing NMDARs. This paradigm is consistent with available data on the sex ratio of live births of women with SLE. It represents a novel mechanism by which maternal autoantibodies can severely affect fetal health in a gender-specific fashion and raises the question of how many maternal antibodies affect brain development or exhibit gender-specific fetal effects.