Reassessment of corticospinal tract regeneration in Nogo-deficient mice.
The myelin-derived neurite growth inhibitor Nogo has been proposed to play a major role in blocking axon regeneration in the CNS after injuries. However, past studies have produced mixed results regarding the regenerative phenotype of various Nogo-deficient mouse lines after experimental spinal cord injury. Two lines did not display enhanced corticospinal tract (CST) regeneration, and one displayed modest regeneration. A fourth line, a Nogo-A,B gene-trap mutant, was instead reported to exhibit extensive CST regeneration, but the results were later found to be inadvertently confounded with an axon labeling artifact. Of the four Nogo mutant lines studied so far, three continue to express some isoform(s) of Nogo, leaving open the question whether any remaining Nogo protein contributes to the modest regenerative phenotype reported in some. The remaining Nogo mutant line studied was confounded by the unexplained rescue of embryonic lethality associated with this mutation. To gain a better understanding of the contribution of Nogo as an inhibitor of regeneration of CNS axons, and particularly CST axons, we reanalyzed the Nogo-A,B gene-trap mutant line and analyzed a novel, fully viable Nogo deletion mutant line that is null for all known isoforms of Nogo. Our analyses failed to reveal any enhanced CST regeneration after experimental spinal cord injury in either line. These results indicate that Nogo alone does not account for lack of CST regeneration and have implications for current therapeutic development for spinal cord injury in humans by targeting Nogo.
Lee
Jae K
JK
Department of Neurosciences, University of California San Diego, School of Medicine, La Jolla, California 92093, USA.
Chan
Andrea F
AF
Luu
Sen M
SM
Zhu
Yuhong
Y
Ho
Carole
C
Tessier-Lavigne
Marc
M
Zheng
Binhai
B
D000483:Alleles; D000818:Animals; D005260:Female; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D009185:Myelin Proteins / Q000172:deficiency* / Q000235:genetics*; D009416:Nerve Regeneration / Q000235:genetics* / Q000502:physiology; D000070798:Nogo Proteins; D011712:Pyramidal Tracts / Q000473:pathology / Q000502:physiology*; D011995:Recombination, Genetic; D013119:Spinal Cord Injuries / Q000235:genetics / Q000503:physiopathology
D009185:Myelin Proteins; D000070798:Nogo Proteins; C000603199:RTN4 protein, human; C000603201:Rtn4 protein, mouse