Abstract Details

Title Oligodendrocyte FGFR2 Conditional Knockout Mice Exhibit a Milder MOG35-55-Induced EAE Disease Course

Topic MS and Related Diseases

Presentation(s) P05 - (-)

Poster/Presentation
Number 166

Objective

Background BACKGROUND: Oligodendrocyte (OL) apoptosis is a key feature of EAE followed by myelin destruction and subsequent axonal damage. FGFR2 plays a critical role in OL proliferation, migration and maturation as well as CNS myelination. We hypothesized that the FGFR2 knock out (KO) mice demonstrate a more severe course of EAE.

Design/Methods DESIGN/METHODS: Using the Cre/lox system on C57BL/6 background, a tamoxifen inducible FGFR2 conditional knockout mouse line (FGFR2-/-) was created under PLP promoter which is specific for OLs. Tamoxifen induction of the FGFR2 KO and MOG35-55-EAE immunization were administrated after 6 and 12 weeks. The clinical score (CS) was assessed until day 60 after immunization, when the mice were sacrificed and subjected to western blot analysis of proteins involved in the signaling pathways of FGFR2.

Results RESULTS: The onset of symptoms at day 8 and the maximum disease severity (CS=4) did not differ between KO mice and controls. FGFR2-/- mice demonstrated an earlier remission (from day 15) compared with the control group (from day 21) (P < 0.05). In contrast to non-EAE mice (both, FGFR2 KO and controls), FGFR2 was up-regulated in EAE populations (mainly in OL rich regions such as spinal cord and hippocampus) (P < 0.05). This up-regulation was less in FGFR2-/- mice, due to conditional KO induction. We also found that the activated extracellular signal-regulated protein kinases 1 and 2 was regulated in a FGFR2-dependant manner in all groups.

Conclusions CONCLUSIONS: This observation in conditional OL FGFR2-/- mice suggest that FGFR2 plays a key role in the pathogenesis of MOG35-55-EAE. However, in contrast to the hypothesis, FGFR2-/- mice were more severely affected.

Authors/Disclosures
Salar Kamali PRESENTER	No disclosure on file
	No disclosure on file
Martin Berghoff, MD, FAAN (BundeswehrZentralkrankenhaus Koblenz)	Dr. Berghoff has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Biogen Idec. Dr. Berghoff has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Roche. Dr. Berghoff has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Janssen. Dr. Berghoff has received personal compensation in the range of $500-$4,999 for serving as a Consultant for MerckSerono. Dr. Berghoff has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Bristol Myers Squibb.
	No disclosure on file
Mark Keegan, MD, FAAN (Mayo Clinic)	Dr. Keegan has received personal compensation in the range of $500-$4,999 for serving as a Consultant for EMD Serono. Dr. Keegan has received publishing royalties from a publication relating to health care. Dr. Keegan has received publishing royalties from a publication relating to health care.
Mark Keegan, MD, FAAN (Mayo Clinic)	Dr. Keegan has received personal compensation in the range of $500-$4,999 for serving as a Consultant for EMD Serono. Dr. Keegan has received publishing royalties from a publication relating to health care. Dr. Keegan has received publishing royalties from a publication relating to health care.

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