An animal model for progressive multifocal leukoencephalopathy
Sheila A. Haley, Walter J. Atwood
Sheila A. Haley, Walter J. Atwood
Published November 17, 2014
Citation Information: J Clin Invest. 2014;124(12):5103-5106. https://doi.org/10.1172/JCI79186.
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Commentary

An animal model for progressive multifocal leukoencephalopathy

Abstract

JC virus (JCV) causes progressive multifocal leukoencephalopathy (PML), a demyelinating disease in humans. The disease, once considered fatal, is now managed with immune reconstitution therapy; however, surviving patients remain severely debilitated. Until now, there has been no animal model to study JCV in the brain, and research into treatment has relied on cell culture systems. In this issue of the JCI, Kondo and colleagues developed a mouse model in which human glial cells are engrafted into neonatal mice that are both immunodeficient and deficient for myelin basic protein. When challenged intracerebrally with JCV, these mice exhibit some of the characteristics of PML. The establishment of this chimeric mouse model is a significant advance toward understanding the mechanism of JCV pathogenesis and the identification of drugs to treat or prevent the disease.

Authors

Sheila A. Haley, Walter J. Atwood

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Figure 1

Chimeric mice provide a murine model of PML.

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Chimeric mice provide a murine model of PML. Human glial progenitor cell...
Human glial progenitor cells are injected into the corpus callosum of neonatal mice. Over the course of 3–4 months, the human glial precursors divide and differentiate into glial cells, such as astrocytes and oligodendrocytes, that incorporate into the murine CNS. Injection of PML-type JCV into the chimeric mouse brain results in infection of human-derived cells, but not murine cells. JCV readily infects and replicates in human glial precursors and human-derived astrocytes. In this model, JCV infects human-derived oligodendrocytes but does not readily replicate in them, instead inducing apoptosis that results in demyelination.