No requirement of alpha-internexin for nervous system development and for radial growth of axons.
Alpha-Internexin is a type IV intermediate filament protein that is expressed abundantly in neurons during development of the peripheral and central nervous systems as well as in few neurons of the adult central nervous system. It has been suggested that alpha-internexin may act as a scaffold for the formation of neuronal intermediate filaments during early development. In addition, recent reports suggest that alpha-internexin could play a major role in two degenerative neurological disorders. We report here an analysis of mice with a targeted disruption of alpha-internexin gene. Unexpectedly, alpha-internexin -/- mice developed normally and did not exhibit overt phenotypes. Moreover, the absence of alpha-internexin did not interfere with neurite extension of cultured DRG neurons. The number and caliber of L4 ventral root axons remained unchanged in alpha-internexin -/- mice. In the retina, alpha-internexin begins to be expressed in retinal ganglion cells when their first axons reach the optic chiasma. Using HRP tracer, we show that the projection pattern of the RGC axons is not modified by the absence of alpha-internexin. Electron microscopy did not reveal significant differences in axonal calibers, in myelination of axons and in neurofilament structures between alpha-internexin -/- and control mice during development and at adult stage. These data indicate that alpha-internexin is not required for the polymerization of neurofilament in vivo. Mice deficient for both alpha-internexin and neurofilament light chain (NF-L) exhibited no over phenotypes as well. No intermediate filament structures were detectable in optic nerve of alpha-internexin -/-; NF-L -/- mice. Ours results do not support the hypothesis of a role for type IV intermediate filaments in axonal outgrowth during development of nervous system.
Levavasseur
F
F
Centre for Research in Neuroscience, McGill University, The Montreal General Hospital Research Institute, L12-218, 1650 Cedar Avenue, Montreal, Quebec, Canada.
Zhu
Q
Q
Julien
J P
JP
D000367:Age Factors; D000818:Animals; D001369:Axons / Q000737:chemistry* / Q000502:physiology* / Q000648:ultrastructure; D015153:Blotting, Western; D001923:Brain Chemistry / Q000502:physiology; D002352:Carrier Proteins / Q000032:analysis / Q000235:genetics*; D018507:Gene Expression Regulation, Developmental; D007381:Intermediate Filament Proteins; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008854:Microscopy, Electron; D009419:Nerve Tissue Proteins / Q000032:analysis / Q000235:genetics*; D016900:Neurofilament Proteins / Q000502:physiology; D009900:Optic Nerve / Q000737:chemistry / Q000166:cytology / Q000254:growth & development; D012333:RNA, Messenger / Q000032:analysis; D012584:Sciatic Nerve / Q000737:chemistry / Q000166:cytology / Q000254:growth & development; D013116:Spinal Cord / Q000737:chemistry / Q000502:physiology
D002352:Carrier Proteins; D007381:Intermediate Filament Proteins; D009419:Nerve Tissue Proteins; D016900:Neurofilament Proteins; D012333:RNA, Messenger; C046643:alpha-internexin; C044882:neurofilament protein L