Proceedings of The Physiological Society
University College London December 2005 (2006) Proc Physiol Soc 1, PC11
Experimental approach to the investigation of human nervous disorders using transgenic or mutant mouse models
Steffens, Heinz; Keller, Bernhard U.; Schomburg, Eike D.;
1. Physiological Institute, University of Goettingen, Goettingen, Germany.
In vitro investigations of transgenic or mutant mouse models with defined neuronal changes revealed valuable insights into pathophysiological mechanisms at the genetic and molecular/cellular level, which may cause motor disorders. The significance of the raised data, however, often remained hypothetical with respect to the in vivo situation of the intact animal and the clinical symptomatology. We now tried to bridge the gap between the findings at the molecular/cellular level and the pathophysiological appearance by analysing the spinal and peripheral components of neuronal disorders with different system-physiological techniques in vivo. Comparative experiments were performed in wild type (WT) mice of the same strain. EMG was recorded in freely moving animals with flexible electrodes implanted into the muscles under ether anaesthesia. Acute experiments were performed in anaesthetized mice (methohexital-Na i.v., 50 mg kg-1 h-1). Body temperature was controlled and ECG was monitored. (1) LDL receptor-related protein 1 (LRP1) knockout mice develop severe behavioural and motor abnormalities. In EMG recordings of freely moving mice of this type a tremor could be demonstrated, which was missing in WT mice (May et al. 2004). (2) In neurexin(1,2,3)
Where applicable, experiments conform with Society ethical requirements