[Abstract Title]. - Society for Neuroscience

Title: Absence of oligodendroglial glucosylceramide synthesis does not cause myelin
abnormalities or change the dysmyelinating phenotype of CGT-deficient mice
Authors: L. SAADAT 1 , G. DAWSON 2 , J. DUPREE 3 , R. PROIA 4 , M. TRAKA 1 , *B. J.
POPKO 1 ;
1 Dept Neurol, 2 Dept Pediatric, Univ. Chicago, Chicago, IL; 3 Dept. of Anat. and Neurobio.,
Virginia Commonwealth Univ., Richmond, VA; 4 Genet. of Develop. and Dis. Branch, Natl. Inst.
of Diabetes and Digestive and Kidney, NIH, Bethesda, MD
Abstract: To examine the function of gangliosides in oligodendrocytes we generated
Ugcg flox/flox ;Cnp/Cre mice, which lack expression of the enzyme UDP-glucose ceramide
glucosyltransferase (Ugcg) specifically in these cells. These mice, which are incapable of
synthesizing glucosylceramide (GlcCer) in their myelinating cells, did not show an abnormal
behavioral or pathological phenotype. Total brain lipid extracts from postnatal day (PND) 18 Wt
and Ugcg flox/flox ;Cnp/Cre mice were analyzed by HPTLC. All GlcCer-based gangliosides
including GM1, GD1a, GD1b, and GT1b showed normal expression levels in the mutant
indicating that oligodendrocytes are not a major source of GlcCer-based ganglioside biosynthesis
in the mouse brain. Preliminary electron microscopy analysis has not revealed any myelin
defects in the CNS of Ugcg flox/flox ;Cnp/Cre mice, indicating that ganglioside elimination in
oligodendrocytes is not detrimental to myelination.
Furthermore, in order to investigate the potential compensatory or toxic effect of the
accumulated hydroxy-fatty-acid-(HFA)-containing GlcCer previously detected in the
galactolipid-deficient (Cgt -/- ) mice (Coetzee, et al 1996 Cell, Vol. 86, 209-219), we generated
Ugcg flox/flox ;Cnp/Cre;Cgt -/- mutants, which are incapable of synthesizing HFA-GlcCer in
oligodendrocytes. The behavioral phenotype of the double mutants was similar to Cgt -/- mice and
morphometric analysis of myelinated fibers in the ventral white matter of the cervical spinal cord
segment showed that both genotypes suffered from the same degree of dysmyelination. Thus,
accumulation of GlcCer in Cgt -/- mice does not appear to functionally compensate for the loss of
the myelin galactolipids or contribute to the pathological defects of the Cgt -/- mice.
Disclosures: L. Saadat, None; J. Dupree, None; R. Proia, None; M. Traka, None; B.J. Popko
, None; G. Dawson, None.
Poster
251. Demyelinating Disorders: Animal Models and Human Studies I
Time: Sunday, November 16, 2008, 1:00 pm - 5:00 pm
Program#/Poster#: 251.8/W1
Topic: C.08.b. Animal models