International Mammalian Genome Society

logo18th International Mouse Genome Conference

17-22 October 2004, Seattle, USA


POSTER 165 - CHARACTERIZATION OF NEW MICE MODELS OF MOTOR NEURON DISEASES

Achilli F 1, Nolan P 2, Fisher EMC 1

1 Institute of Neurology, London, United Kingdom, 2 MRC Mammalian Genetic Unit, Harwell, United Kingdom

The aim of this study is to characterize three mutant mice lines (GENA201, 202 and BHV/7) with motor deficits as assessed in the primary screen of the Harwell ENU Mutagenesis Programme. For the purpose of this motor neuron disorder study, we have adopted four parameters to assess the motor coordination and the balance of the three mouse strains The parameters measured include grip strength, rotarod performance, wire manoeuvre and weight from ages 1-12 months.

Following phenotyping at 5, 9, 15 weeks and 7 months, GENA 201 and 202 mutants showed poor grip strength. The results also showed no correlation between grip strength and rotarod performances and poor correlation between grip strength and wire manoeuvre. No significant weight loss was observed in the mice. General tremor was the only visible phenotype observed concurrent with poor grip strength.

On the other hand, BHV/7 mutants showed a very clear phenotype including retropulsion, hyperactivity and aggression. Due to their aggressive and hyperactive behaviour, it was very difficult to characterize their locomotor behaviour.BHV/7 mutants were significantly lighter than wild type but there was no statistical difference between mutants and wild type in the grip strength performance.

These results allow the scoring of mutant and wild type mice in order to map and subsequently clone the defective genes. As the BHV/7 mutants could be easily scored visibly due to their distinctive phenotype, a genome scan was performed.

Gaining access to new genes involved in the pathology of motor neurons will provide the opportunity to investigate the biology of MND so that it will be possible to identify and characterize novel genetic defects associated with motor MND.

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