Could mutations in PLP initiate MS?

Dr Judith Greer

University of Queensland, QLD

| Causes and Prevention | Immunology | Incubator | 2011 | Investigator Led Research |


Myelin proteolipid protein (PLP) is the most abundant protein component of central nervous system myelin and is essential for maintenance and structure of the myelin. The gene that makes PLP, ‘PLP1’, is located on the X chromosome, with mutations manifesting in males as Pelizaeus-Merzbacher disease (PMD), where myelin production is highly disrupted. Females are generally non-symptomatic carriers, as they carry two copies of the X chromosome and usually only one carries the mutation.

However, two recent reports described individuals diagnosed with MS who also carry PLP1 gene mutations. These mutations differ from those found to cause PMD. How these mutations may relate to the development of MS in these individuals is unclear. We know from research in PMD that some mutations in the PLP1 gene can cause PLP protein to accumulate within the body of myelin producing cells (oligodendrocytes), causing damage and even death of these cells. This study investigates whether or not the PLP1 gene mutations that have been found in MS patients could directly damage oligodendrocytes, and therefore contribute to disease development.

Progress to Date

To complete this objective Ms Moxy has made cells that are producing PLP from either the normal PLP1 gene or one of five genetic variations of PLP1, each of which contains a different gene mutation. Three of these PLP1 gene mutations have been reported in people with MS, and the other two are found in people with PMD and serve as controls. Nancy is looking at changes to cell health and the level of protein produced. Dr Greer and Ms Moxey have been able to show that the PMD mutations kill the cells, whereas the mutations from people with MS are not so damaging to the cells, although the cells do not look completely healthy. Nancy is finalising the studies measuring the effects of the PLP1 gene mutations on cell health, but the data so far suggests that some of the PLP1 gene mutations that have been found in people with MS can cause damage.

Updated: 3 July 2012

Updated: 03 January, 2011


  • Dr Judith Greer, University of Queensland, QLD
  • Ms Nancy Moxey, University of Queensland, QLD

Grant Awarded

  •  Incubator Grant

Total Funding

  • $24,500


  • 1 year over 2011

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Could mutations in PLP initiate MS?