Multiple sclerosis genetic insight

18 May 2005

A study published in the current edition of Science reports the discovery that a gene called Olig 1 is essential for the repair of myelin in diseases of the central nervous system (CNS) such as multiple sclerosis (MS), which affects around 85,000 people in the UK and 2.5 million worldwide. Myelin is a fatty substance that surrounds and effectively insulates nerves cells in the brain and spinal cord and allows rapid transmission of nervous impulses from brain to muscle. When the myelin sheath becomes damaged, as in MS and other forms of demyelinating disease, neural transmission is impaired with debilitating results, such as difficulty in walking, impaired vision, bladder and bowel dysfunction and altered cognitive function (eg. defective memory). MS typically begins as a series of attacks interspersed with complete or partial remissions when damaged nerves become recovered with myelin. Eventually the ongoing repair process seems to break down and over time the disease tends to follow a progressively worsening course. Researchers from the Centre for Brain Repair and the School of Veterinary Medicine at the University of Cambridge and the Dana-Farber Institute at Harvard University have found that the Olig1 gene controls a process that can restore myelination of nerve fibres [Arnett HA et al. (2004) Science 306, 2111-2115].

Olig1 and Olig2 are closely related transcription factors (proteins that bind to DNA in the cell nucleus and regulate expression of particular genes) present in mature oligodendrocytes, nerve cells that produce myelin in the CNS. To investigate the functions of these genes, the researchers used antibodies against the Olig proteins to identify their location in oligodendrocytes in mice at different stages of CNS development. Olig2 was localised to the cell nucleus throughout, as expected for a transcription factor, whereas the Olig1 proteins became progressively located in the cytoplasm as the cells matured into myelin producing oligodendrocytes. This differential localization of Olig1 and Olig2 was also seen in the adult human brain.

Next, using rodent models of induced myelin injury and regeneration, it was found that Olig1 proteins were present in the nucleus of cells in remyelinating lesions. Post-mortem adult brain tissue from MS patients showed that Olig1 was present in the cytoplasm of cells in normal, healthy areas of white matter, but largely in the nucleus of cells at the edges of damaged areas where remyelination would be expected to occur. This finding was therefore taken to be consistent with movement of Olig1 to the cell nucleus as part of the myelin repair process in MS patients. The researchers also looked at mice in which the Olig1 and Olig2 genes were absent. Olig2

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