Genetic analysis of myelin galactolipid function.
The CGT enzyme is responsible for catalyzing the final step in GalC synthesis. The isolation of the CGT cDNA has allowed for the genetic analysis of galactolipid function by providing the opportunity to generate null mutants deficient in CGT enzymatic activity. The detailed analyses of CGT mutant mice demonstrate that the galactolipids are essential for the formation and maintenance of normal CNS myelin, but neither GalC or sulfatide appear to be required for the development of structurally normal PNS myelin. These studies also show that the differentiation of myelinating cells is not dependent on galactolipid function, in contrast to the conclusions drawn from prior antibody perturbation studies. The abnormal node of Ranvier formations present in the CNS likely explain the disrupted electrophysiological properties displayed by mutant spinal cord axons and the tremoring phenotype of these mice. The abnormal myelin structures present in the mutant animals are consistent with the possibility that the galactolipids play a role in regulating or mediating proper axo-glial interactions. The further detailed analysis of these animals should help refine our understanding of galactolipid function in the myelination process.
Popko
B
B
Neuroscience Center, University of North Carolina at Chapel Hill 27599, USA. bpopko@css.unc.edu
Dupree
J L
JL
Coetzee
T
T
Suzuki
K
K
Suzuki
K
K
D000818:Animals; D005700:Galactosyltransferases / Q000172:deficiency / Q000235:genetics* / Q000378:metabolism; D051147:Ganglioside Galactosyltransferase; D051379:Mice; D018345:Mice, Knockout; D009186:Myelin Sheath / Q000473:pathology / Q000502:physiology; D011901:Ranvier's Nodes / Q000473:pathology*
D005700:Galactosyltransferases; C511214:Ugt8a protein, mouse; D051147:Ganglioside Galactosyltransferase