Assessment of functional recovery and axonal sprouting in oligodendrocyte-myelin glycoprotein (OMgp) null mice after spinal cord injury.
Oligodendrocyte-myelin glycoprotein (OMgp) is a myelin component that has been shown in vitro to inhibit neurite outgrowth by binding to the Nogo-66 receptor (NgR1)/Lingo-1/Taj (TROY)/p75 receptor complex to activate the RhoA pathway. To investigate the effects of OMgp on axon regeneration in vivo, OMgp(-/-) mice on a mixed 129/Sv/C57BL/6 (129BL6) or a C57BL/6 (BL6) genetic background were tested in two spinal cord injury (SCI) models - a severe complete transection or a milder dorsal hemisection. OMgp(-/-) mice on the mixed 129BL6 genetic background showed greater functional improvement compared to OMgp(+/+) littermates, with increased numbers of cholera toxin B-labeled ascending sensory axons and 5-HT(+) descending axons and less RhoA activation after spinal cord injury. Myelin isolated from OMgp(-/-) mice (129BL6) was significantly less inhibitory to neurite outgrowth than wild-type (wt) myelin in vitro. However, OMgp(-/-) mice on a BL/6 genetic background showed neither statistically significant functional recovery nor axonal sprouting following dorsal hemisection.
Ji
Benxiu
B
Department of Discovery Biology, Biogen Idec Inc., 14 Cambridge Center, Cambridge MA 02142, USA.
Case
Lauren C
LC
Liu
Kai
K
Shao
Zhaohui
Z
Lee
Xinhua
X
Yang
Zhongshu
Z
Wang
Joy
J
Tian
Tim
T
Shulga-Morskaya
Svetlana
S
Scott
Martin
M
He
Zhigang
Z
Relton
Jane K
JK
Mi
Sha
S
D000704:Analysis of Variance; D000818:Animals; D001369:Axons / Q000502:physiology*; D001710:Biotin / Q000031:analogs & derivatives / Q000378:metabolism; D002772:Cholera Toxin / Q000378:metabolism; D003911:Dextrans / Q000378:metabolism; D005106:Exploratory Behavior / Q000502:physiology; D005260:Female; D007839:Functional Laterality / Q000235:genetics; D058851:GPI-Linked Proteins; D005727:Ganglia, Spinal / Q000473:pathology; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009185:Myelin Proteins; D018992:Myelin-Associated Glycoprotein / Q000172:deficiency*; D063308:Myelin-Oligodendrocyte Glycoprotein; D016501:Neurites / Q000502:physiology; D009474:Neurons / Q000473:pathology; D020127:Recovery of Function / Q000235:genetics / Q000502:physiology*; D012701:Serotonin / Q000378:metabolism; D013119:Spinal Cord Injuries / Q000473:pathology* / Q000503:physiopathology*; D013997:Time Factors; D020742:rhoA GTP-Binding Protein / Q000378:metabolism
D003911:Dextrans; D058851:GPI-Linked Proteins; D005904:Glial Fibrillary Acidic Protein; C571327:Mog protein, mouse; D009185:Myelin Proteins; D018992:Myelin-Associated Glycoprotein; D063308:Myelin-Oligodendrocyte Glycoprotein; C560529:Omg protein, mouse; C076397:biotinylated dextran amine; D012701:Serotonin; D001710:Biotin; D002772:Cholera Toxin; D020742:rhoA GTP-Binding Protein