INCREASED ACCUMULATION OF TRANSFERRIN BY MOTOR-NEURONS OF THE MOUSE MUTANT PROGRESSIVE MOTOR NEURONOPATHY (PMN/PMN)

It has been suggested that iron-carrying transferrin exerts growth-factor-like influences on motor neurons. I have evaluated the distribution of proteins related to the intracerebral iron-homeostasis in the mouse mutant progressive motor neuronopathy (pmn/pmn); an autosomal recessive mutant with progressive caudo-cranial motor neuron degeneration. A higher immunoreactivity of transferrin and transferrin receptor in motor neurons of the pmn/pmn mutant compared to that in normal mice was demonstrated. Ferritin was not observed in motor neurons of the pmn/pmn mutant. Transferrin receptors were absent from axons and neuromuscular junctions, indicating that entry of blood-borne, liver-derived transferrin ('liver transferrin') into motor neurons due to uptake and subsequent retrograde axonal transport was unspecific. Due to the selective presence of transferrin receptors on neuronal somata, a more likely mode of entry of transferrin into the motor neurons was by receptor-mediated uptake of brain-derived transferrin ('brain transferrin') at the soma. This study provides data on transferrin accumulation and transferrin receptor expression in diseased motor neurons and adds further insights into influences of proteins related to iron-homeostasis in the diseased PNS.