Experimental allergic encephalomyelitis in connexin 43-heterozygous mice.
Alterations in the expression of gap junction proteins (connexins) have previously been observed in experimental allergic encephalomyelitis (EAE). Demyelinating lesions have significantly decreased Cx43, while recovering lesions have greatly increased Cx43 and increased glial fibrillary acidic protein-expressing astrocytes. This suggests an important role for gap-junctional intercellular communication in astrocytes in the recovery from CNS inflammation. To study the effects of decreased Cx43 expression during acute disease (21 days post-immunization) and in recovering spinal cord tissue (55 days post-immunization) we induced EAE in Cx43 heterozygous and wild-type mice. Mice showed signs of disease by day 10, and signs of recovery by day 25. There were no clinical or pathological differences between heterozygous and wild-type mice in the acute disease stage, except that wild-type male mice had fewer clinical signs of disease. Male mice that were heterozygous for Cx43, and therefore had decreased expression of Cx43, had increased EAE disease severity. All demyelinating lesions had reduced numbers of reactive astrocytes and a significant decrease in Cx43 expression. In the 55-day study, all heterozygous and wild-type mice were clinically improved, showed decreased pathological signs, and showed increased laminin expression, indicative of CNS recovery. Furthermore, all heterozygous mice showed a striking increase in Cx43 expression during recovery, suggesting that the regulatory factors affecting Cx43 expression are still present in mice that have only one wild-type Cx43 allele.
Department of Physiology and Pharmacology, University of Western Ontario, London, Ontario, Canada.
W A
WA
Roscoe
G M
GM
Kidder
S J
SJ
Karlik
D000818:Animals; D020169:Caspases / Q000378:metabolism; D018031:Connexin 43 / Q000235:genetics*; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000473:pathology*; D005260:Female; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D006579:Heterozygote; D007797:Laminin / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D012727:Sex Characteristics
D018031:Connexin 43; D005904:Glial Fibrillary Acidic Protein; D007797:Laminin; D020169:Caspases