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The Journal of Neuroscience, July 15, 2002, 22(14):6041-6051

Myelination Is Altered in Insulin-Like Growth Factor-I Null Mutant Mice

Ping Ye¹, Liqin Li¹, R. Gregg Richards², Richard P. DiAugustine², and A. Joseph D'Ercole¹

¹ Department of Pediatrics, The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, and ² Hormones and Cancer Group, National Institute of Environmental Health Sciences, Triangle Research Park, North Carolina 27709

Increasing evidence indicates that insulin-like growth factor-I (IGF-I) has an important role in oligodendrocyte development. In this study, we examined myelination during postnatal development in IGF-I knock-out (KO) mice by assessing myelin staining, the expression of myelin basic protein (MBP) and proteolipid protein (PLP), two major myelin-specific proteins, and the number of oligodendrocytes and their precursors. For comparison, we also measured the expression of median subunit of the neuron-specific intermediate filament, M-neurofilament (M-NF), to obtain an index of the effects of IGF-I deficiency on neurons. We found that myelin staining, MBP and PLP expression, and the percentage of oligodendrocytes and their precursors are significantly reduced in all brain regions of developing IGF-I KO mice but are similar to controls in adult IGF-I KO mice. In contrast, the abundance of M-NF was decreased in both the developing and adult brain of IGF-I KO mice. We also found that IGF-II protein abundance is increased in the brains of IGF-I KO mice. Our data indicate, therefore, that myelination during early development is altered in the absence of IGF-I by mechanisms that involve a reduction in oligodendrocyte proliferation and development. Although neuronal actions cannot be excluded in the myelin normalization, the reduced axonal growth suggested by the reduced M-NF expression makes a role for neuronal factors less compelling. These data suggest that IGF-I plays a significant role in myelination during normal early development and that IGF-II can compensate in part for IGF-I actions on myelination.

Key words: IGF-I; IGF-II; oligodendrocytes; oligodendrocyte precursors; myelination; development

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Copyright © 2002 Society for Neuroscience  0270-6474/02/22146041-11$05.00/0

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