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Research Article Free access | 10.1172/JCI118821

Neutrophil infiltration, glial reaction, and neurological disease in transgenic mice expressing the chemokine N51/KC in oligodendrocytes.

M Tani, M E Fuentes, J W Peterson, B D Trapp, S K Durham, J K Loy, R Bravo, R M Ransohoff, and S A Lira

Department of Neurosciences, Research Institute, Cleveland Clinic Foundation, Cleveland, Ohio 44195, USA.

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Department of Neurosciences, Research Institute, Cleveland Clinic Foundation, Cleveland, Ohio 44195, USA.

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Department of Neurosciences, Research Institute, Cleveland Clinic Foundation, Cleveland, Ohio 44195, USA.

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Department of Neurosciences, Research Institute, Cleveland Clinic Foundation, Cleveland, Ohio 44195, USA.

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Department of Neurosciences, Research Institute, Cleveland Clinic Foundation, Cleveland, Ohio 44195, USA.

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Department of Neurosciences, Research Institute, Cleveland Clinic Foundation, Cleveland, Ohio 44195, USA.

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Department of Neurosciences, Research Institute, Cleveland Clinic Foundation, Cleveland, Ohio 44195, USA.

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Department of Neurosciences, Research Institute, Cleveland Clinic Foundation, Cleveland, Ohio 44195, USA.

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Department of Neurosciences, Research Institute, Cleveland Clinic Foundation, Cleveland, Ohio 44195, USA.

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Published July 15, 1996 - More info

Published in Volume 98, Issue 2 on July 15, 1996
J Clin Invest. 1996;98(2):529–539. https://doi.org/10.1172/JCI118821.
© 1996 The American Society for Clinical Investigation
Published July 15, 1996 - Version history
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Abstract

Chemokines (pro-inflammatory chemoattractant cytokines) are expressed in pathological conditions of the central nervous system (CNS). Previous studies suggested that the CNS is relatively resistant to leukocyte diapedesis after chemokine injection, leaving their functional role unresolved. The CNS function of N51/KC, a neutrophil-selective chemokine, was addressed by expressing N51/KC under control of the myelin basic protein (MBP) promoter in transgenic (tg) mice (MBP-N51/KC mice). CNS-specific N51/KC expression produced remarkable neutrophil infiltration into perivascular, meningeal, and parenchymal sites, demonstrating that this chemokine exerts the multiple functions in vivo required to recruit leukocytes into the CNS. MBP-N5 1/KC mice represent an incisive model for the molecular dissection of neutrophil entry into the CNS. Unexpectedly, MBP-N51/KC mice developed a neurological syndrome of pronounced postural instability and rigidity at high frequency beginning at 40 days of age, well after peak chemokine expression. 68/182 mice in one tg fine were found dead before one year of age, with prominent neurological symptoms premortem in 26 (38%). Florid microglial activation and blood-brain barrier disruption without dysmyelination were the major neuropathological alterations. Late-onset neurological symptoms in MBP-N51/KC mice may indicate unanticipated consequences of CNS chemokine expression.

Version history
  • Version 1 (July 15, 1996): No description
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