Cuprizone Mouse Models of Multiple Sclerosis (MS)

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