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Macromolecular structure of axonal membrane in the optic nerve of the jimpy mouse
J A Black1, R D Fields, S G Waxman
1Department of Neurology, Yale University School of Medicine, New Haven, CT 06510.
Abstract:
The macromolecular structure of the axon membrane in 26-28-day-old Jimpy mice and control optic nerve were examined with quantitative freeze-fracture electron microscopy. Premyelinated and myelinated axons were observed in control optic nerves, with axonal diameters of premyelinated axons being generally smaller than that of myelinated axons (approximately 0.2-0.4 micron vs approximately 0.5-1.5 micron, respectively). Axon membrane from control optic nerves exhibited an asymmetrical partitioning of intramembranous particles (IMP). P-faces of internodal membrane displayed nearly twice as many IMP as the premyelinated axolemma (1,731 vs 893 micron-2, respectively). E-faces of internodal and premyelinated axolemma exhibited IMP densities of 124 and 157 micron-2, respectively. Few myelinated axons were apparent in optic nerves from Jimpy mice. The amyelinated axons of Jimpy mice displayed a spectrum of axonal diameters, ranging from approximately 0.2 to 1.5 micron. P-face densities of amyelinated axons, considered as a group, exhibited a wide range (600-2,100 micron-2). However, large diameter (greater than or equal to 0.5 micron) axons exhibited a significantly greater P-face IMP density than that of small caliber (greater than 0.5 micron) axons (1,525 vs 1,032 micron-2, respectively). Aggregations of E-face IMP were not observed along amyelinated axons of Jimpy optic nerves. The results demonstrate that the changes in P-face IMP density that occur during development of normal myelinated axons also occur in developing axons of Jimpy optic nerve, irrespective of a lack of normal glial cell association, and provide further evidence that the primary defect of hypomyelination within Jimpy mice is not attributed to the neuron.
Insights
Jimpy mice, despite lacking normal myelination, show similar axon membrane particle changes as developing control mice. This suggests the neuron is not the primary cause of hypomyelination in Jimpy mice.
Area of Science:
- Neuroscience
- Cell Biology
- Biophysics
Background:
- The Jimpy mouse model exhibits a severe hypomyelination defect.
- Understanding the molecular basis of myelination is crucial for neurological research.
- Axon membrane structure and function are critical for nerve impulse transmission.
Purpose of the Study:
- To investigate the macromolecular structure of axon membranes in Jimpy mice compared to controls.
- To determine if developmental changes in intramembranous particle (IMP) density occur in Jimpy axons.
- To assess whether neuronal defects contribute to hypomyelination in Jimpy mice.
Main Methods:
- Quantitative freeze-fracture electron microscopy was used.
- Axon membrane structure was analyzed in optic nerves of 26-28-day-old Jimpy and control mice.
- Intramembranous particle (IMP) density on P-faces and E-faces was quantified.
Main Results:
- Control optic nerves showed myelinated and premyelinated axons with asymmetrical IMP distribution.
- Jimpy mice had amyelinated axons with a wide range of IMP densities.
- Large diameter Jimpy axons (>0.5 micron) had significantly higher P-face IMP density than small diameter axons.
- IMP density changes in Jimpy axons mirrored those in developing normal myelinated axons.
Conclusions:
- Axon membrane IMP density changes during development occur in Jimpy mice, independent of normal myelination.
- The neuron itself is unlikely to be the primary defect causing hypomyelination in Jimpy mice.
- Findings support a glial cell defect as the cause of hypomyelination in Jimpy mice.