Houenou_1996_J.Neuropathol.Exp.Neurol_55_698

The survival and morphometric characteristics of lumbar spinal motoneurons were examined in the paralyse mouse mutant. Affected (par/par) mice can be first recognized at approximately postnatal day (PN) 7 to 8 and are characterized by their smaller-than-normal body size, a progressive generalized muscle weakness, and lack of coordination. Mutant mice die by PN16-18, when they have become almost completely paralyzed. Previously, we have shown that this mutation involves alteration of several developmental aspects of the neuromuscular system. However, whether ventral (or anterior) horn motoneurons degenerate and die during the course of the disease was unknown. We report here that at the time the mutant phenotype can be first identified (i.e. approximately PN8), lumbar motoneuron numbers in the lateral motor column of the spinal cord of paralyse mice were not significantly different from those of control littermates. In contrast, by PN14, there was a significant (30 to 35%) decrease in motoneuron numbers in mutant compared to control mice. Furthermore, motoneuron (nuclear and soma) sizes were significantly decreased in the mutants at both stages examined, i.e. PN8 and PN14. These results show that the paralyse mutation involves atrophy and subsequent death of anterior horn motoneurons. Together with the rapid progression and the severity of the disease, these results suggest that the paralyse mouse may represent a good animal model for studying early-onset human motor neuron diseases such as spinal muscular atrophy.