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Title: Neurobiology of oligodendrocytes in the PLP mutant rumpshaker
Author: Fanarraga, Monica Lopez
Awarding Body: University of Glasgow
Current Institution: University of Glasgow
Date of Award: 1993
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The jprsh is a murine recessive X-linked point mutation of the PLP gene characterised by a single amino-acid substitution (Ile186 → Thr). Affected hemizygous males and homozygous females showed tremor and ataxia of the hindlimbs. No seizures, infertility or premature death of the animals occurred. Morphological examination of the jprsh mutant CNS tissue revealed a noticeable hypomyelination which included abnormally thin and vacuolated myelin sheaths, intermingled with unmyelinated axons. There were appropriate oligodendrocytes numbers at the time of myelination, in fact, cell counts were highter than for the wild type in the spinal cord and were increasing progressively with age. Older mice demonstrated a gradual myelin production the spinal cord. Immunocytochemistry of jprsh CNS tissue revealed a defect in the production of PLP while myelin sheaths immunostained intensely for DM-20. Quantification of the PLP/DM-20 mRNA levels indicated that the PLP expression in individual cells was decreased, particularly in younger mutants. However, the total number of PLP/DM-20 expressing cells was higher than for age-matched wild type mice. PLP/DM-20 mRNA levels did not correlate with the final low amounts of protein. The ability of jprsh oligodendrocytes to differentiate was assessed by staining cell dissociations form the optic nerves and spinal cord taken from mice at different ages and cultured for variable lengths of time with specific antigenic markers. Mutant oligodendrocytes differentiated normally to the GAlC stage. The number of MBP immunostained cells was decreased, particularly when mutant oligodendrocytes developed in vitro although the expression in individual cells was normal. The immunoreactivity against C-terminal antibody recognizing both PLP and DM-20 was also decreased. However, PLP/DM-20+ mutant cells immunostained at the appropriate time. O10, PLP and O11 indicative of the most mature stages in wild type oligodendrocytes, were virtually absent. Finally, 3H-thymidine labelling in the spinal cord revealed that jprsh oligodendrocytes, identified by morphological and PLP expression, divide well into adulthood probably contributing to the delayed myelination of the spinal cord. Asymptomatic heterozygote jprsh females did not reveal the predictable histological mosaic myelination pattern observed for the other PLP mutant heterozygotes.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available