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The Journal of Neuroscience, August 20, 2003, 23(20):7710-7718

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Insulin-Like Growth Factor (IGF) Signaling through Type 1 IGF Receptor Plays an Important Role in Remyelination

Jeffrey L. Mason,¹ Shouhong Xuan,² Ioannis Dragatsis,² Argiris Efstratiadis,² and James E. Goldman¹

¹Department of Pathology and The Center for Neurobiology and Behavior, and ²Department of Genetics and Development, Columbia University, New York, New York 10032

We examined the role of IGF signaling in the remyelination process by disrupting the gene encoding the type 1 IGF receptor (IGF1R) specifically in the mouse brain by Cre-mediated recombination and then exposing these mutants and normal siblings to cuprizone. This neurotoxicant induces a demyelinating lesion in the corpus callosum that is reversible on termination of the insult. Acute demyelination and oligodendrocyte depletion were the same in mutants and controls, but the mutants did not remyelinate adequately. We observed that oligodendrocyte progenitors did not accumulate, proliferate, or survive within the mutant mice, compared with wild type, indicating that signaling through the IGF1R plays a critical role in remyelination via effects on oligodendrocyte progenitors.

Key words: demyelination; oligodendrocyte; progenitors; apoptosis; macrophages; transgenic

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Received Apr. 10, 2003; revised Jun. 11, 2003; accepted Jul. 7, 2003.

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