Connexins are critical for normal myelination in the CNS.
Mutations in Cx32, a gap-junction channel-forming protein, result in X-linked Charcot-Marie-Tooth disease, a demyelinating disease of the peripheral nervous system. However, although oligodendrocytes express Cx32, central myelination is unaffected. To explore this discrepancy, we searched for additional oligodendrocyte connexins. We found Cx47, which is expressed specifically in oligodendrocytes, regulated in parallel with myelin genes and partially colocalized with Cx32 in oligodendrocytes. Mice lacking either Cx47 or Cx32 are viable. However, animals lacking both connexins die by postnatal week 6 from profound abnormalities in central myelin, characterized by thin or absent myelin sheaths, vacuolation, enlarged periaxonal collars, oligodendrocyte cell death, and axonal loss. These data provide the first evidence that gap-junction communication is crucial for normal central myelination.
Menichella
Daniela M
DM
Department of Neurobiology, Harvard Medical School, Boston, Massachusetts 02115, USA.
Goodenough
Daniel A
DA
Sirkowski
Erich
E
Scherer
Steven S
SS
Paul
David L
DL
D000818:Animals; D015153:Blotting, Western; D002490:Central Nervous System / Q000378:metabolism* / Q000473:pathology; D002607:Charcot-Marie-Tooth Disease / Q000235:genetics; D017630:Connexins / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D003711:Demyelinating Diseases / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology; D018450:Disease Progression; D017629:Gap Junctions / Q000378:metabolism; D007150:Immunohistochemistry; D051379:Mice; D018345:Mice, Knockout; D009186:Myelin Sheath / Q000378:metabolism*; D009836:Oligodendroglia / Q000378:metabolism / Q000473:pathology; D009900:Optic Nerve / Q000378:metabolism / Q000473:pathology; D012333:RNA, Messenger / Q000378:metabolism; D013116:Spinal Cord / Q000378:metabolism / Q000473:pathology; D000097002:Gap Junction beta-1 Protein
D017630:Connexins; D012333:RNA, Messenger; D000097002:Gap Junction beta-1 Protein; C427305:connexin 47