Mice lacking NT-3, and its receptor TrkC, exhibit profound deficiencies in CNS glial cells

Authors

  • M.A. Kahn,

    1. Mental Retardation Research Center, Departments of Neurobiology and Psychiatry, Brain Research Institute, UCLA School of Medicine, Los Angeles, California
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  • S. Kumar,

    1. Mental Retardation Research Center, Departments of Neurobiology and Psychiatry, Brain Research Institute, UCLA School of Medicine, Los Angeles, California
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  • D. Liebl,

    1. Center for Developmental Biology, University of Texas Southwestern Medical Center, Dallas, Texas
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  • R. Chang,

    1. Mental Retardation Research Center, Departments of Neurobiology and Psychiatry, Brain Research Institute, UCLA School of Medicine, Los Angeles, California
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  • L.F. Parada,

    1. Center for Developmental Biology, University of Texas Southwestern Medical Center, Dallas, Texas
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  • J. De Vellis

    Corresponding author
    1. Mental Retardation Research Center, Departments of Neurobiology and Psychiatry, Brain Research Institute, UCLA School of Medicine, Los Angeles, California
    • Mental Retardation Research Center 760 Westwood Plaza, Rm. 68–225, NPI, Los Angeles, CA 90024–1759.
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Abstract

Neurotrophin-3 (NT-3) and its receptor TrkC are known to be important for neuronal survival. More recently, NT-3 has been implicated as playing a role in oligodendrocyte (OL) proliferation and survival in vitro. Examination of NT-3 and TrkC knockout mice revealed a reduction in NT-3-dependent neurons. To date, no study has examined alterations in glial cell populations in these knockout mice. In this report, we demonstrate a decline in OL progenitor cell numbers within the CNS of NT-3 and TrkC knockout mice. We also observed that immature and mature OL-specific markers were attenuated in the NT-3 and TrkC knockout animals. Deficiencies in other CNS glial cells, including astrocytes and ameboid microglia, were also observed. The subventricular zone (SVZ), a highly proliferative region for progenitor glial cells, was reduced in size. Furthermore, a nuclear-specific stain revealed a decline in the numbers of pyknotic nuclei in and around the SVZ of the knockout mice. These data will support an in vivo NT-3-dependent mechanism for the normal development of CNS glial cells. GLIA 26:153–165, 1999. © 1999 Wiley-Liss, Inc.

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