Behavioural profiling of a murine Charcot-Marie-Tooth disease type 1A model

Different features of motor behaviour were studied on a transgenic mouse mo del of Charcot-Marie-Tooth's disease (CMT). Mutants with 4 or 7 copies of t he human PMP22 gene leading to a phenotype significantly close to CMT's dis ease type 1A were compared with control animals. The aim of the study was t o validate this transgenic model and to characterise the impairments occurr ing in the various lines. Three main types of analysis were performed in 2- month-old mice without any peculiar visible deficit: (i) a study of standar dised clinical tests (SHIRPA protocol) demonstrated that only a few motor d eficits were expressed; (ii) a measurement of general spontaneous activity by means of a commercial video-tracking system was performed and revealed t hat the main spontaneous activities were identical in the three lines with, however, some slight localised modifications; and, (iii) by contrast, the three lines respond very differently to the footprints, grip strength, spla y test and rotarod test. Even in lines with a significantly limited copy nu mber of the transgene, we observed and quantified impairments. In conclusio n, mutants of CMT1A seem to be a very pertinent model of this human patholo gy and will certainly be useful for therapeutic procedures and for theoreti cal studies on this disease.