Macrophage-related demyelination in peripheral nerves of mice deficient in the gap junction protein connexin 32.
Mice deficient in the gap junction protein connexin 32 (Cx32) develop a slowly progressing demyelinating neuropathy, with enlarged periaxonal collars, abnormal non-compacted myelin domains and axonal sprouts. These mice serve as a model for the X-linked form of inherited demyelinating neuropathies in humans. Based on our previous findings that macrophages are involved in demyelination in other myelin mutants (i.e. mice heterozygously deficient in P0), we considered the possibility that macrophages might be also mediators of demyelination in Cx32-deficient mice. Indeed, we detected an age-related increase in the number of macrophages in demyelinating nerves of Cx32-deficient mice. In addition, immunoelectron microscopy revealed macrophages in an apposition to degenerating myelin reminiscent of a macrophage-mediated demyelinating neuropathy. We conclude that involvement of macrophages might be a widespread phenomenon in genetically-determined demyelination.
Kobsar
Igor
I
Department of Neurology, Section of Developmental Neurobiology, University of Wurzburg, Josef-Schneider-Strasse 11, D-97080 Wurzburg, Germany.
Mäurer
Mathias
M
Ott
Thomas
T
Martini
Rudolf
R
D000818:Animals; D000943:Antigens, Differentiation / Q000378:metabolism; D001369:Axons / Q000378:metabolism / Q000473:pathology / Q000648:ultrastructure; D002452:Cell Count; D017630:Connexins / Q000172:deficiency* / Q000235:genetics; D005260:Female; D017629:Gap Junctions / Q000235:genetics* / Q000473:pathology / Q000648:ultrastructure; D007150:Immunohistochemistry; D008264:Macrophages / Q000378:metabolism* / Q000473:pathology / Q000648:ultrastructure; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D008854:Microscopy, Electron; D018993:Myelin P0 Protein / Q000172:deficiency / Q000235:genetics; D010525:Peripheral Nerves / Q000378:metabolism* / Q000473:pathology / Q000648:ultrastructure; D011129:Polyradiculoneuropathy / Q000235:genetics* / Q000276:immunology / Q000473:pathology; D012583:Schwann Cells / Q000378:metabolism / Q000473:pathology / Q000648:ultrastructure; D015854:Up-Regulation / Q000235:genetics / Q000276:immunology; D000097002:Gap Junction beta-1 Protein
D000943:Antigens, Differentiation; D017630:Connexins; D018993:Myelin P0 Protein; D000097002:Gap Junction beta-1 Protein; C036763:monocyte-macrophage differentiation antigen