A Dopamine-Sensitive Inherited Motor Syndrome Linked to the frissonnant Mutation-

Authors
N. Callizot, J.-L. Guenet, P. Poindron.

Lab
Université Louis-Pasteur, Faculté de Pharmacie, Laboratoire de Pathologie des Communications entre Cellules Nerveuses et Musculaires, Strasbourg, France.

Journal
New Animal Models of Human Neurological Diseases.

Abstract
The frissonnant (fri) mutation is an autosomal recessive mutation which spontaneously appeared in 1977 in the stock of C3H mice of the Pasteur Institute in Paris. fri/fri mutation causes locomotor instability and rapid tremor. The tremor ceases when mutated animals sleep or are anaesthetized. In the light of these symptoms, it seems that fri/fri shares similarities with human Parkinson disease (PD). Here we give a precise and full description of the fri phenotype with an accurate behavioural, electrophysiological and histological analysis. The results show that fri/fri mice present an important motor deficit with visible tremor and stereotypies. We observed that fri/fri mice display some memory deficits as in human PD. We also show thatL-3,4-dihydroxyphenylananine and apomorphine (dopaminergic agonists), ropinirole (selective D2 agonist) and selegiline (a monoamine oxidase B inhibitor) improve the clinical status of these animals. Finally, we found that fri/fri mice did not display any anatomopathological evidence of nigrostriatal lesion nor a decrease in tyrosine hydroxylase production. We conclude that fri/fri mice present a dopamine-sensitive inherited motor syndrome associated with a parkinsonian syndrome, but are not a mouse model of PD disease. They could be used as a tool for studying and screening dopaminergic compounds with central activity.

BIOSEB Instruments Used:
Aron Test or Four Plates Test (LE830),Rotarod (BX-ROD)