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)± (essential for Ca²⁺-triggered neurotransmitter release) double knockout mice the tetanic isometric contraction force was reduced (40% at 62 Hz) compared to WT mice. (3) Heterozygous mice with reduced axonal neuregulin-1 (NRG1+/-) expression show decreased myelin sheath thickness (average g-ratio increased from 0.66 to 0.79) without a change of the axonal diameter and the internodal length (Michailov et al. 2004). Despite the reduced myelin sheath there was no significant change of the peripheral nervous conduction velocity (range of values for WT vs NRG1+/-): fastest group I: 40-52 m s^-1 vs 42-55 m s^-1; group II and III: 9-34 m s^-1 vs 10-40 m s^-1; group IV: 0.7-0.9 m s^-1 vs 0.8-0.9 m s^-1; group A±: 33-50 m s^-1 vs 41-60 m s^-1; group A³: 13-27 m s^-1 vs 12-25 m s^-1. (4) In SOD1-G93A mice (model for the familial amyotrophic lateral sclerosis) at an age of 98-120 days, a higher reflex fatigability was particularly observed at higher stimulation frequencies (>4 s^-1), average reduction compared to WT >50%. In younger SOD1-G93A mice there was no reduction observable, in older mice the reflexes were abolished. The mouse models proved to provide a useful link between the molecular/cellular level and the clinical appearance of human nervous disorders and may thus serve as a helpful tool to test therapeutical approaches in an acute experiment.