The development and pathogenesis of the sensory neuropathy in the mutant rat mf.

A study was made of the development of sensory pathways in the mutant rat mutilated foot (mf) which is affected by a sensory neuropathy with autosomal recessive inheritance. Microscopic abnormalities are well recognizable at the fifteenth embryonic day. By day 16, dorsal root ganglia are smaller than normal and show more numerous foci of cell necrosis which continue throughout the remainder of gestation and during the first and second postnatal days. During this period the number of ganglion cells decreases sharply. Reconstruction of cell volumes shows that the larger cells are more severely affected. The secondary sensory nuclei (gracile nuclei) are normal at birth but during the first two postnatal weeks become progressively smaller than in normal rats. The results suggest that the mutant gene acts primarily on the dorsal root ganglia causing excessive neuronal cell death. Qualitatively, the events in this mutant are closely similar to 'programmed cell death' in the normal. It is likely that neurons of second order nuclei, which are not contacted by afferent fibres, undergo a process of transneuronal degeneration as a secondary effect of excessive ganglion cell loss.