CaltechTHESIS
  A Caltech Library Service

Biochemical and Genetic Studies of Peripheral Myelination in Normal Development and in the Mouse Mutant Trembler

Citation

Fryxell, Karl Joseph (1983) Biochemical and Genetic Studies of Peripheral Myelination in Normal Development and in the Mouse Mutant Trembler. Dissertation (Ph.D.), California Institute of Technology. doi:10.7907/eahp-bx93. https://resolver.caltech.edu/CaltechTHESIS:10112019-091636747

Abstract

I developed a radioimmunoassay for P0, the major peripheral myelin protein, and adapted an existing radioimmunoassay for myelin basic protein. Results from these assays showed that Schwann cells do not make either protein before myelination begins, and accumulate P0 and myelin basic protein with the same time course during development. Schwann cells cultured in the absence of neurons do not express detectable levels of either protein, but they do continue to synthesize sulfatide, a myelin sulfolipid, apparently indefinitely, as shown by biosynthetic labeling.

The trembler (Tr/+) mouse mutant has a pronounced reduction in peripheral myelin, while central myelin and peripheral unmyelinated nerves appear normal. This myelin deficiency is caused by an autonomous Schwann cell defect. Since the Trembler phenotype is expressed in heterozygotes, most previous studies were confined to Tr/+ mice. Using two alleles, I show here that the six possible genotypes can be ordered as follows: +/+ > Trj/+ > Tr/+ > Trj/Trj > Trj/Tr > Tr/Tr, based on myelin basic protein radioimmunoassays of sciatic nerve extracts. The amount of compact myelin in each genotype, as shown by electron microscopy, is in good agreement with the radioimmunoassay results, with two important provisos. First, Tr/Tr mice have 1% of wild-type myelin basic protein levels but essentially no compact myelin. Secondly, the first steps in the above genetic series reduce both the average myelin sheath area and the number of myelin sheaths by similar amounts, while the last steps primarily reduce the number of myelin sheaths. These results suggest that, if the activity of the Tr+ gene product is reduced below a certain point, myelin protein synthesis can be induced without forming a myelin sheath. Visualization of P0 by indirect immunofluorescence shows that Schwann cells without compact myelin express much lower levels of P0 than adjacent Schwann cells, associated with the same axon, that do form compact myelin. Finally, although Trembler Schwann cells proliferate excessively in vivo, their proliferation is not affected by Tr gene dose. In vitro Trj/Trj Schwann cell proliferation is apparently normal. Thus, it is likely that the function of the Tr+ gene product is not directly concerned with Schwann cell proliferation.

Item Type:Thesis (Dissertation (Ph.D.))
Subject Keywords:Biology
Degree Grantor:California Institute of Technology
Division:Biology
Major Option:Biology
Thesis Availability:Public (worldwide access)
Research Advisor(s):
  • Revel, Jean-Paul
Thesis Committee:
  • Revel, Jean-Paul (chair)
  • Hood, Leroy E.
  • Hudspeth, A. James
  • Owen, Ray David
Defense Date:17 May 1983
Funders:
Funding AgencyGrant Number
NSFUNSPECIFIED
NIHUNSPECIFIED
Evelyn Sharp FoundationUNSPECIFIED
Jean Weigle Memorial FundUNSPECIFIED
Record Number:CaltechTHESIS:10112019-091636747
Persistent URL:https://resolver.caltech.edu/CaltechTHESIS:10112019-091636747
DOI:10.7907/eahp-bx93
Related URLs:
URLURL TypeDescription
https://doi.org/10.1111/j.1471-4159.1980.tb09026.xDOIArticle adapted for Chapter 1.
https://doi.org/10.1111/j.1471-4159.1983.tb11316.xDOIArticle adapted for Chapter 2.
Default Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:11812
Collection:CaltechTHESIS
Deposited By: Melissa Ray
Deposited On:16 Oct 2019 14:27
Last Modified:19 Apr 2021 22:38

Thesis Files

[img]
Preview
PDF - Final Version
See Usage Policy.

28MB

Repository Staff Only: item control page