The Contribution of Connexin 43 in Choroid Plexus to Experimental Autoimmune Encephalomyelitis

Abstract Multiple Sclerosis (MS) is the most common progressive neurologic disease among young adults worldwide; yet the pathogenesis remains poorly understood. The myelin oligodendrocyte glycoprotein (MOG)-induced experimental autoimmune encephalitis (EAE) in mice is a robust model and has been extensively used to understand the pathophysiology of MS. The expression of connexin 43 (CX43), a gap junction protein, has been shown to be enhanced in the choroid plexus during the development of acute EAE, with significantly increased CX43 expression at the peak of the disease. However, the contribution of such increased CX43 expression to the development of EAE has yet to be fully characterized. Using the Cre-Lox platform, we generated mice with conditional deletion of CX43 in the ciliated columnar epithelium of the choroid plexus (Foxj1Cre-CX43 KO mice; referred to as CX43 KO mice hereafter). We employed the MOG-induced EAE model in both male and female CX43 KO mice to understand the role of CX43 in the pathogenesis of EAE. Male CX43 and WT mice displayed comparable peak EAE clinical disease scores of 1.83±0.33 and 1.75±0.66, respectively. Female CX43 KO, however, displayed a significantly reduced peak EAE clinical disease score of 0.33±0.24 compared to 1.15±0.39 in female WT animals. These results suggest a role for CX43 in the ciliated columnar epithelium of choroid plexus to the development of EAE in female, not male, mice and underscore the need for further exploration of mechanism(s) underpinning the role of CX43 in the pathogenesis of EAE.