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Demyelination in a transgenic mouse: a model for multiple sclerosis
F G Mastronardi1, C A Ackerley, L Arsenault
1Department of Biochemistry, Hospital for Sick Children, Toronto, Canada.
Journal of Neuroscience Research
|October 15, 1993
Summary
Transgenic mice with excess DM20 (a myelin protein) developed demyelination and neurological symptoms. This suggests persistent immature myelin in adults causes myelin disruption and disease.
Area of Science:
- Neuroscience
- Genetics
- Cell Biology
Background:
- Myelin proteolipid protein (PLP) is crucial for myelin sheath integrity.
- DM20 is a splice variant of PLP, abundant in young myelin.
- Overexpression of myelin components can lead to neurological dysfunction.
Purpose of the Study:
- To investigate the effects of high-level DM20 expression on myelin development and neurological function.
- To determine if DM20 overexpression causes demyelination in a transgenic mouse model.
Main Methods:
- Generated transgenic mice (ND4) with 70 copies of the DM20 transgene.
- Clinical assessment of neurological symptoms (tremors, gait) at different ages.
- Quantification of myelin content and PLP levels.
- Histological and electron microscopic analysis for demyelination, astrogliosis, and cellular infiltration.
- Optic nerve examination.
Main Results:
- ND4 mice showed normal development until 3 months, followed by tremors and death by 8-10 months.
- Significant reduction in myelin content (17% of normal) by 10 months.
- Progressive astrogliosis and evidence of disrupted myelin with astrocyte phagocytosis.
- Lymphocytic infiltration observed.
- Optic nerves showed denuded and thinly myelinated axons.
Conclusions:
- High DM20 expression leads to progressive demyelination and neurological deficits in adult mice.
- Persistence of immature myelin composition into adulthood results in myelin instability.
- Demyelination in ND4 mice is linked to the failure of myelin maturation.