Motoneuron Morphological Alterations Before and after the Onset of the Disease in the Wobbler Mouse

The wobbler mutant mouse displays a recessively inherited neurological disease with degeneration of motoneurons and is considered to be an animal model for human motoneuron diseases. Mutant mice can be clinically recognised at about 3-4 weeks of age but a polymorphic marker close to the wobbler gene offers the opportunity of a preclinical diagnosis. Using this polymorphic marker we performed morphometric (cell size) analysis of spinal cord motoneurons from 10 to 40 days post natal (PN). We observed at day 16 PN a transient appearance of swollen motoneurons, probably those that present vacuolar degeneration a little later and possibly die. One week later, from 21 days onwards, we found that the subpopulation of large motoneurons was depleted in the mutant mice. The absence of large motoneurons may have important physiological consequences and the loss or absence of differentiation of this particular subpopulation of motoneurons may be a key event in the course of the disease.