Patients' resources > Genetic animal models of migraine: what do they tell us?

Genetic animal models of migraine: what do they tell us?

Genetic abnormalities that headache investigators are identifying more and more at an increasing rate may certainly help explain why the disease occurs as an unexpected, isolated condition in some cases, while in others it follows a predictable pattern. However, they tell us very little about other fundamental aspects of migraine genetics: how can genetic abnormalities cause the disease? Which mediators do they operate through? What mechanisms are involved?

These questions may be much more easily answered through test animal models exhibiting gene mutations that are similar to those found in patients with migraine.

Recently, the Dutch research group leading the Eurohead Project created a specific "knock-in" mouse strain1, i.e. one in which the same gene mutation found in familial hemiplegic migraine (R192Q) had been induced with genetic engineering techniques. Studying this so-called transgenic animal enabled researchers to find out that the gene mutation typically occurring in patients with familial hemiplegic migraine is associated with an increased likelihood of neuronal firing in specific brain areas. The "fired" neurones would then carry messages to other neurones, as a result of some modification affecting the flow of calcium ions through cell membranes. Besides causing changes in the behaviour of brain neurones, this gene mutation in mice would also increase the release of neurotransmitters in those areas where nerves come into contact with muscles, i.e. neuromuscular junctions.

Genetic animal models of migraine can therefore be said to play a major key role in improving the understanding of the neurochemical and, above all, functional implications of genome abnormalities associated with certain migraine forms.

References

1. van den Maagdenberg AM, Pietrobon D, Pizzorusso T, Kaja S, Broos LA, Cesetti T, van de Ven RC, Tottene A, van der Kaa J, Plomp JJ, Frants RR, Ferrari MD. A Cacna1a knockin migraine mouse model with increased susceptibility to cortical spreading depression. Neuron. 2004;41:701-10

This page last modified: 08/07/2005