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Updated: Jul 20, 2026
In vivo Imaging of Optic Nerve Fiber Integrity by Contrast-Enhanced MRI in Mice
Published on: July 22, 2014
T(2)-weighted microMRI and evoked potential of the visual system measurements during the development of
Melanie Martin1, Samuel D Reyes, Timothy D Hiltner
1Department of Physics, University of Winnipeg, 515 Portage Avenue, Winnipeg, Manitoba, Canada, R3B 2E9. m.martin@uwinnipeg.ca
Abstract:
Our objective was to follow the course of a dysmyelinating disease followed by partial recovery in transgenic mice using non-invasive high-resolution (117 x 117 x 70 microm) magnetic resonance (microMRI) and evoked potential of the visual system (VEP) techniques. We used JOE (for J37 golli overexpressing) transgenic mice engineered to overexpress golli J37, a product of the Golli-mbp gene complex, specifically in oligodendrocytes. Individual JOE transgenics and their unaffected siblings were followed from 21 until 75-days-old using non-invasive in vivo VEPs and 3D T2-weighted microMRI on an 11.7 T scanner, performing what we believe is the first longitudinal study of its kind. The microMRI data indicated clear, global hypomyelination during the period of peak myelination (21-42 days), which was partially corrected at later ages (>60 days) in the JOE mice compared to controls. These microMRI data correlated well with [Campagnoni AT (1995) "Molecular biology of myelination". In: Ransom B, Kettenmann H (eds) Neuroglia--a Treatise. Oxford University Press, London, pp 555-570] myelin staining, [Campagnoni AT, Macklin WB (1988) Cellular and molecular aspects of myelin protein gene-expression. Mol Neurobiol 2:41-89] a transient intention tremor during the peak period of myelination, which abated at later ages, and [Lees MB, Brostoff SW (1984) Proteins in myelin. In: Morell (ed) Myelin. Plenum Press, New York and London, pp 197-224] VEPs which all indicated a significant delay of CNS myelin development and persistent hypomyelination in JOE mice. Overall these non-invasive techniques are capable of spatially resolving the increase in myelination in the normally developing and developmentally delayed mouse brain.
Insights
This study used advanced magnetic resonance imaging and visual evoked potential techniques to track a dysmyelination and recovery process in JOE transgenic mice, revealing delayed central nervous system myelin development.
Area of Science:
- Neuroscience
- Developmental Biology
- Biophysics
Background:
- Oligodendrocytes are crucial for central nervous system (CNS) myelination.
- Dysmyelinating diseases disrupt the formation and maintenance of myelin sheaths.
- Genetic engineering allows for the creation of mouse models to study myelin disorders.
Purpose of the Study:
- To longitudinally investigate a dysmyelinating disease with partial recovery in transgenic mice.
- To assess the efficacy of non-invasive magnetic resonance imaging (microMRI) and visual evoked potential (VEP) techniques in tracking myelination dynamics.
- To characterize the phenotype of JOE transgenic mice overexpressing golli J37 in oligodendrocytes.
Main Methods:
- Utilized high-resolution 3D T2-weighted microMRI (11.7 T scanner) for in vivo imaging.
- Employed non-invasive visual evoked potentials (VEPs) to assess visual system function.
- Conducted a longitudinal study from 21 to 75 days of age in JOE transgenic mice and controls.
Main Results:
- microMRI revealed global hypomyelination in JOE mice during peak myelination (21-42 days), with partial correction by >60 days.
- VEPs indicated significant delays in CNS myelin development and persistent hypomyelination.
- Observed a transient intention tremor in JOE mice, correlating with the myelination period.
Conclusions:
- Non-invasive microMRI and VEPs are effective for spatially resolving myelination changes in developing mouse brains.
- JOE transgenic mice exhibit a dysmyelinating phenotype with delayed myelination and partial recovery.
- These findings highlight the utility of advanced imaging techniques for studying neurological development and disease.
