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Cuprizone Model Overview

The cuprizone multiple sclerosis mouse model of demyelination and remyelination is induced by feeding mice the copper-chelating cuprizone toxin. Cuprizone administration in mice models several aspects of human multiple sclerosis (MS), including central nervous system (CNS) loss of myelin, spontaneous remyelination, oligodendrocyte precursor cell (OPC) proliferation & maturation to myelinating oligodendrocytes, astrogliosis, and microgliosis. The myelin pathology and associated neuroinflammation observed in the cuprizone model in mice is most prominent the corpus callosum with highly predictable pathology that mimics MS lesions. Learn more in our Resource - Demyelination & Remyelination in the Cuprizone Model.

Unlike EAE, the cuprizone model of multiple sclerosis is not autoimmune mediated and the cuprizone induced white matter demyelination and remyelination are not confounded by a peripheral immune response. EAE and cuprizone mice model different aspects of MS pathology, and therapeutic studies are often performed in parallel.

Cuprizone Model Generation

  • C57BL/6 mice are fed 0.2-0.3% cuprizone via diet (powdered chow or food pellets) or oral gavage to induce toxicity to mature oligodendrocytes and damage to the myelin sheath
  • A more severe, chronic, mouse demyelination model can be generated by injecting rapamycin (i.p. 5 days per week)
  • In our experience, the powdered chow diet route of administration provides the most reproducible results

Our Validated Cuprizone Mouse Model Measures

  • Body weight
  • Myelin-sensitive in vivo magnetic resonance imaging (MRI)
  • Immunohistochemistry & multiplex immunofluorescence for myelin, oligodendrocyte precursor cells (OPCs), mature oligodendrocytes, and neuroinflammation (microglia & astrocytes) in the corpus callosum
Two brain cross-sections stained for Myelin Basic Protein (MBP), used in studying demyelination in a cuprizone mouse model of Multiple Sclerosis (MS), with varying levels of myelin indicated by the staining intensity

Myelin Basic Protein (MBP) immunohistochemistry (IHC) staining of the corpus callosum in control mice (top) and mice after 5 weeks of cuprizone diet treatment (bottom).

Learn more about our characterization of this model, our validated measures, and our Preclinical Neuroscience CRO services.

Discover more about our Multiple Sclerosis Models

FAQs

What are the advantages of in vivo MRI for the cuprizone mouse model?


What is the typical time course of demyelination and remyelination in the cuprizone model in mice?


Is inflammation observed in the cuprizone mouse model?


Can cuprizone and EAE studies be performed in parallel?


What is the cuprizone-rapamycin mouse model?


Related Content

Up-to-date information on Multiple Sclerosis and best practices related to the evaluation of therapeutic agents in MS animal models.

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