THE PARALYSE-MOUSE MUTANT - A NEW ANIMAL-MODEL OF ANTERIOR HORN MOTOR-NEURON DEGENERATION

The survival and morphometric characteristics of lumbar spinal motoneu rons were examined in the paralyse mouse mutant. Affected (par/par) mi ce can be first recognized at approximately postnatal day (PN) 7 to 8 and are characterized by their smaller-than-normal body size, a progre ssive generalized muscle weakness, and lack of coordination. Mutant mi ce die by PN16-18, when they have become almost completely paralyzed. Previously, we have shown that this mutation involves alteration of se veral developmental aspects of the neuromuscular system. However, whet her ventral (or anterior) horn motoneurons degenerate and die during t he course of the disease was unknown. We report here that at the time the mutant phenotype can be first identified (i.e. similar to PN8), lu mbar motoneuron numbers in the lateral motor column of the spinal cord of paralyse mice were not significantly different from those of contr ol littermates. In contrast, by PN14, there was a significant (30 to 3 5%) decrease in motoneuron numbers in mutant compared to control mice. Furthermore, motoneuron (nuclear and soma) sizes were significantly d ecreased in the mutants at both stages examined, i.e. PN8 and PN14. Th ese results show that the paralyse mutation involves atrophy and subse quent death of anterior horn motoneurons. Together with the rapid prog ression and the severity of the disease, these results suggest that th e paralyse mouse may represent a good animal model for studying early- onset human motor neuron diseases such as spinal muscular atrophy.