Spatiotemporal progression of neurodegeneration and glia activation in thewobbler neuropathy of the mouse

THE wobbler mouse (phenotype WR; genotype wr/wr) has been investigated as a model for neurodegenerative diseases like SMA and ALS. A new; diagnostic m arket based on a polymorphism in the closely linked chaperonine gene Cct4 e nabled us to diagnose the allelic status at the wr locus within the origina l background-strain C57BL/6. Using this marker, we investigated the spatiot emporal progression of neuropathology in WR mice from postnatal day (d.p.n. ) 10 to 60. Neurodegeneration starts at 13 d.p.n. in the thalamus (N. ventr alis), in deep cerebellar nuclei, brain stem (N. vestibularis) and spinal c ord interneurons. The motor nuclei of spinal nerves and motoneurons degener ate from 15 d.p.n. onward. Reactive astrocytes are observed around 17 d.p.n . in the white and grey matter of the spinal cord. Microgliosis occurs only from 23 d.p.n. onward. Our data demonstrate that in the WR disease, neurod egeneration in thalamus, cerebellum and brain stem precedes motoneuron dege neration, astrogliosis and;microgliosis. NeuroReport 10:3411-3416 (C) 1999 Lippincott Williams & Wilkins.