T2-weighted μMRI and Evoked Potential of the Visual System Measurements During the Development of Hypomyelinated Transgenic Mice
Our objective was to follow the course of a dysmyelinating disease followed by partial recovery in transgenic mice using non-invasive high-resolution (117 × 117 × 70 μm) magnetic resonance (μMRI) 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 μMRI on an 11.7 T scanner, performing what we believe is the first longitudinal study of its kind. The μMRI 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 μMRI 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.
KeywordsGolli products Myelin basic protein J37 Magnetic resonance imaging VEP Myelination Dysmyelination Myelin Golli–mbp
The authors would like to acknowledge funding from the NIH NEI (R01-EY011933) and NINDS (R01-NS23022 and R01-NS46337) and NSERC and Xiaowei Zhang for assistance with MRI.
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