RGD Reference Report - Deoxyribozyme-mediated knockdown of xylosyltransferase-1 mRNA promotes axon growth in the adult rat spinal cord. - Rat Genome Database

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Deoxyribozyme-mediated knockdown of xylosyltransferase-1 mRNA promotes axon growth in the adult rat spinal cord.

Authors: Hurtado, A  Podinin, H  Oudega, M  Grimpe, B 
Citation: Hurtado A, etal., Brain. 2008 Oct;131(Pt 10):2596-605. Epub 2008 Sep 2.
RGD ID: 2313145
Pubmed: PMID:18765417   (View Abstract at PubMed)
DOI: DOI:10.1093/brain/awn206   (Journal Full-text)

In the injured spinal cord, proteoglycans (PGs) within scar tissue obstruct axon growth through their glycosaminoglycan (GAG)-side chains. The formation of GAG-side chains (glycosylation) is catalysed by xylosyltransferase-1 (XT-1). Here, we knocked down XT-1 mRNA using a tailored deoxyribozyme (DNAXTas) and hypothesized that this would decrease the amount of glycosylated PGs and, consequently, promote axon growth in the adult rat spinal cord. A continuous 2-week delivery of DNAXTas near the rostral border of a peripheral nerve graft bridging the transected dorsal columns in the thoracic spinal cord resulted in an 81% decrease in XT-1 mRNA, an average of 1.4-fold reduction in GAG-side chains of chondroitin sulphate or heparan sulphate-PGs and 2.2-fold reduction in neurocan and brevican core proteins in scar tissue. Additionally, compared to control deoxyribozyme, the DNAXTas treatment resulted in a 9-fold increase in length and a 4-fold increase in density of ascending axons growing through the nerve graft and scar tissue present at the rostral spinal cord. Together our data showed that treatment with a deoxyribozyme against XT-1 mRNA decreased the amount of glycosylated PGs and promoted axon growth through scar tissue in the injured spinal cord. The deoxyribozyme approach may become a contributing factor in spinal cord repair strategies.



RGD Manual Disease Annotations    Click to see Annotation Detail View

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
XYLT1HumanSpinal Cord Injuries  ISOXylt1 (Rattus norvegicus) RGD 
Xylt1RatSpinal Cord Injuries  IMP  RGD 
Xylt1MouseSpinal Cord Injuries  ISOXylt1 (Rattus norvegicus) RGD 

Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
Xylt1Ratnegative regulation of axon regeneration  IMP  RGD 

Objects Annotated

Genes (Rattus norvegicus)
Xylt1  (xylosyltransferase 1)

Genes (Mus musculus)
Xylt1  (xylosyltransferase 1)

Genes (Homo sapiens)
XYLT1  (xylosyltransferase 1)


Additional Information