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 x 117 x 70 mu m) magnetic resonance (mu MRI) 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 mu MRI on an 11.7 T scanner, performing what we believe is the first longitudinal study of its kind. The mu MRI 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 mu MRI 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.