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dc.contributor.authorMoutal, Aubin
dc.contributor.authorKalinin, Sergey
dc.contributor.authorKowal, Kathy
dc.contributor.authorMarangoni, Natalia
dc.contributor.authorDupree, Jeffrey
dc.contributor.authorLin, Shao Xia
dc.contributor.authorLis, Kinga
dc.contributor.authorLisi, Lucia
dc.contributor.authorHensley, Kenneth
dc.contributor.authorKhanna, Rajesh
dc.contributor.authorFeinstein, Douglas L
dc.date.accessioned2020-01-29T22:20:27Z
dc.date.available2020-01-29T22:20:27Z
dc.date.issued2019-12-03
dc.identifier.citationMoutal, A., Kalinin, S., Kowal, K., Marangoni, N., Dupree, J., Lin, S. X., … Feinstein, D. L. (2019). Neuronal Conditional Knockout of Collapsin Response Mediator Protein 2 Ameliorates Disease Severity in a Mouse Model of Multiple Sclerosis. ASN Neuro, 11, 175909141989209. https://doi.org/10.1177/1759091419892090 ‌en_US
dc.identifier.issn1759-0914
dc.identifier.pmid31795726
dc.identifier.doi10.1177/1759091419892090
dc.identifier.urihttp://hdl.handle.net/10150/636775
dc.description.abstractWe previously showed that treatment with lanthionine ketimine ethyl ester (LKE) reduced disease severity and axonal damage in an experimental autoimmune encephalomyelitis (EAE) mouse model of multiple sclerosis and increased neuronal maturation and survival in vitro. A major target of LKE is collapsin response mediator protein 2 (CRMP2), suggesting this protein may mediate LKE actions. We now show that conditional knockout of CRMP2 from neurons using a CamK2a promoter to drive Cre recombinase expression reduces disease severity in the myelin oligodendrocyte glycoprotein (MOG)35–55 EAE model, associated with decreased spinal cord axonal damage, and less glial activation in the cerebellum, but not the spinal cord. Immunohistochemical staining and quantitative polymerase chain reaction show CRMP2 depletion from descending motor neurons in the motor cortex, but not from spinal cord neurons, suggesting that the benefits of CRMP2 depletion on EAE may stem from effects on upper motor neurons. In addition, mice in which CRMP2 S522 phosphorylation was prevented by substitution for an alanine residue also showed reduced EAE severity. These results show that modification of CRMP2 expression and phosphorylation can influence the course of EAE and suggests that treatment with CRMP2 modulators such as LKE act in part by reducing CRMP2 S522 phosphorylation.en_US
dc.description.sponsorshipNational Multiple Sclerosis Society [RG-1501-02654]; US Department of Veteran Affairs [14S-RCS-003]; United States Department of Health & Human Services National Institutes of Health (NIH) - USA [1R01NS098772, 1R01DA042852]en_US
dc.language.isoenen_US
dc.publisherSAGE PUBLICATIONS LTDen_US
dc.rightsCopyright © The Author(s) 2019. Creative Commons Non Commercial CC BY-NC: This article is distributed under the terms of the Creative Commons AttributionNonCommercial 4.0 License (https://creativecommons.org/licenses/by-nc/4.0/).en_US
dc.rights.urihttps://creativecommons.org/licenses/by-nc/4.0/
dc.subjectCRMP2en_US
dc.subjectEAEen_US
dc.subjectLKEen_US
dc.subjectmultiple sclerosisen_US
dc.subjectspinal corden_US
dc.subjectupper motor neuronsen_US
dc.titleNeuronal Conditional Knockout of Collapsin Response Mediator Protein 2 Ameliorates Disease Severity in a Mouse Model of Multiple Sclerosisen_US
dc.typeArticleen_US
dc.contributor.departmentUniv Arizonaen_US
dc.identifier.journalASN NEUROen_US
dc.description.noteOpen access journalen_US
dc.description.collectioninformationThis item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at repository@u.library.arizona.edu.en_US
dc.eprint.versionFinal published versionen_US
dc.source.journaltitleASN neuro
refterms.dateFOA2020-01-29T22:20:27Z


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Copyright © The Author(s) 2019. Creative Commons Non Commercial CC BY-NC: This article is distributed under the terms of the Creative Commons AttributionNonCommercial 4.0 License (https://creativecommons.org/licenses/by-nc/4.0/).
Except where otherwise noted, this item's license is described as Copyright © The Author(s) 2019. Creative Commons Non Commercial CC BY-NC: This article is distributed under the terms of the Creative Commons AttributionNonCommercial 4.0 License (https://creativecommons.org/licenses/by-nc/4.0/).