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-fac tor-like influences on motor neurons. I have evaluated the distributio n of proteins related to the intracerebral iron-homeostasis in the mou se mutant progressive motor neuronopathy (pmn/pmn); an autosomal reces sive mutant with progressive caudo-cranial motor neuron degeneration. A higher immunoreactivity of transferrin and transferrin receptor in m otor neurons of the pmn/pmn mutant compared to that in normal mice was demonstrated. Ferritin was not observed in motor neurons of the pmn/p mn mutant. Transferrin receptors were absent from axons and neuromuscu lar junctions, indicating that entry of blood-borne, liver-derived tra nsferrin ('liver transferrin') into motor neurons due to uptake and su bsequent retrograde axonal transport was unspecific. Due to the select ive presence of transferrin receptors on neuronal somata, a more likel y 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 tra nsferrin receptor expression in diseased motor neurons and adds furthe r insights into influences of proteins related to iron-homeostasis in the diseased PNS.