   2.8.2.11 | more |
a sulfatide (ST)-deficient mouse model is generated by disrupting the gene that encodes the enzyme cerebroside sulfotransferase (CST) that catalyzes the last step of ST biosynthesis. CST knockout (CST-/-) mice, which show a complete loss of ST in brain tissue, are born healthy, but begin displaying hindlimb weakness and tremors by 4-6 weeks of age. These defects aggravate with age, causing pronounced tremor and eventual ataxia, that lead to partial or complete paralysis by 12 months of age and eventually result in premature death which typically occurs around 15 months. Molecular fingerprints underlying the myelin phenotypes are described for CST KO mice, including (1) a one-third loss of compact-myelin proteins and major myelin lipids, presumably due to the loss of negative charges from ST species, (2) a striking post-developmental loss of MAG and NF155, and (3) a progressive loss of intermolecular PLP interactions. The tremor and ataxic phenotypes that occur in the absence of ST are a consequence of the loss of NF155 and PLP intermolecular interactions. Loss of ST results in reduced GalCer synthesis and/or increased GalCer degradation. ST depletion leads to a post-developmental disruption of myelin sphingolipid homeostasis. ST depletion leads to a dramatic and progressive loss of NF155 in every CNS region analyzed |
761717 |
