RETINAL DEGENERATION IN THE NERVOUS MUTANT MOUSE .2. ELECTRON-MICROSCOPIC ANALYSIS

Nervous mutant mice (nr/nr) show a rapid loss of most of cerebellar Pu rkinje cells between the ages of 3 and 7 weeks, as well as a progressi ve photoreceptor cell degeneration that occurs most rapidly between po stnatal days (P) 13 and 19, but with a much slower attrition during th e subsequent months. We have carried out an electron microscopic analy sis of nr/nr and littermate control mice at representative ages to cha racterize the subcellular cytopathological changes in this form of ret inal degeneration, to gain insight into photoreceptor cell degeneratio n mechanisms by comparing these changes to those in other rodent forms of retinal degeneration, and to compare the photoreceptor changes wit h those of cerebellar Purkinje cells. Ultrastructural observations wer e limited to rod photoreceptors, since the number of cones was limited in our micrographs. The retinas of nr/nr mutant mice can be distingui shed from those of normal littermates as early as postnatal day (P) 6. At this time, some of the mitochondria in rod inner segments are larg er and more rounded than normal. This represents the earliest cytopath ological change thus far observed in this mutant. As early as P9 and t hereafter, the volume and integrity of rod outer segment membranes are reduced from normal. In the inner segments of some rod photoreceptor cells, there is a reduction in the volume or number of polyribosomes a s early as P11, a reduction in rough endoplasmic reticulum as early as P13, and reduced incidence and less organized Golgi membranes as earl y as P16. Qualitative evaluation and quantitative stereological analys is show that the enlarged mitochondria in rod inner segments never bec ome normal in shape or size. No changes are seen in the inner retinal layers at any age. Despite similarities with inherited retinal dystrop hy in the Royal College of Surgeons rat, as noted in the original desc ription of retinal degeneration in nr/nr mice, ultrastructural feature s clearly distinguish these mutants. Moreover, nr/nr mice can be disti nguished from all other murine forms of retinal degeneration by electr on microscopy.