title: In vitro death of jimpy oligodendrocytes: correlation with onset of DM-20/PLP expression and resistance to oligodendrogliotrophic factors.
abstract: Severe hypomyelination in the jimpy (jp) mouse mutation results from premature death of most oligodendrocytes (OCs). We have applied an immunopanning technique to successfully purify oligodendroblasts (OBs) directly from neonatal jp brainstem in order to determine if their death during differentiation into OCs is preventable in culture by diffusible oligodendrogliotrophic factors. No significant differences in the yield (0.9-1.1 x 10(5) cells/brainstem) or viability (approximately 90%) of OB populations from jp and wild-type (wt) littermates were observed, indicating that cell death occurs at a later stage in the mutant lineage. When cultured in a basally defined, insulin-containing medium, wt and jp OBs died 1-2 days later as their differentiation into GalC+ OCs began. Survival was not enhanced by known trophic factors (ciliary neurotrophic factor, leukemia inhibitory factor, neurotrophin-3) for differentiating rat OCs. In medium conditioned by neonatally derived rat or wt mouse astrocytes, however, wt OBs survived terminal OC differentiation, expressing first GalC, then DM-20/PLP on their surface 1-2 days later, before elaborating myelin-like membrane. By contrast, jp OBs in sister cultures survived differentiation initially as well as their normal counterparts did but rapidly died thereafter, beginning at the time when PLP/DM-20 immunoreactivity became detectable on premature wt GalC+ OCs. Additionally under these conditions, there survived a minor population (<5%) of jp cells, including mature OCs, which expressed stunted membranes and DM-20/PLP immunoreactivity in their cytoplasm, and undifferentiated progenitors. This model supports the concept that OC death in jp is effected by an intrinsic program, one mechanistically related to jp PLP/DM-20 gene expression and refractory to trophic cues in the environment.
authors.affiliation: Department of Structural and Cellular Biology, College of Medicine, University of South Alabama, Mobile 36688-0002, USA.
authors.forename: W C
authors.initials: WC
authors.lastname: Williams
authors.forename: A L
authors.initials: AL
authors.lastname: Gard
mesh_terms: D000818:Animals; D000831:Animals, Newborn / Q000502:physiology; D001059:Apoproteins / Q000235:genetics / Q000378:metabolism*; D001253:Astrocytes / Q000378:metabolism; D001921:Brain / Q000166:cytology; D016923:Cell Death / Q000502:physiology; D002454:Cell Differentiation / Q000502:physiology; D002478:Cells, Cultured; D016922:Cellular Senescence / Q000502:physiology; D017077:Culture Media, Conditioned / Q000494:pharmacology; D016895:Culture Media, Serum-Free; D015870:Gene Expression / Q000502:physiology; D051379:Mice; D008815:Mice, Inbred Strains; D008816:Mice, Jimpy / Q000502:physiology*; D018991:Myelin Proteolipid Protein / Q000235:genetics / Q000378:metabolism*; D009414:Nerve Growth Factors / Q000502:physiology*; D009419:Nerve Tissue Proteins; D009836:Oligodendroglia / Q000502:physiology*; D051381:Rats; D013045:Species Specificity
chemical_list: D001059:Apoproteins; D017077:Culture Media, Conditioned; D016895:Culture Media, Serum-Free; D018991:Myelin Proteolipid Protein; D009414:Nerve Growth Factors; D009419:Nerve Tissue Proteins; C047516:Plp1 protein, mouse; C489071:Plp1 protein, rat