THE EFFECT OF THE MOUSE MUTATION CLAW PAW ON MYELINATION AND NODAL FREQUENCY IN SCIATIC-NERVES

Despite the biophysical and clinical importance of differentiating nod al and internodal axolemma, very little is known about the process. We chose to study myelination and node of Ranvier formation in the hypom yelinating mouse mutant claw paw (clp). The phenotype of clp is delaye d myelination in the peripheral nervous system. The specific defect is unknown but is thought to arise from a breakdown in the complex signa ling mechanism between axon and Schwann cell. Myelination was assessed in sciatic nerve cross sections from adult and postnatal day 14 (P14) heterozygous and homozygous clp mice. Antibodies to PO, myelin-associ ated glycoprotein (MAG), and neural cell adhesion molecule were used t o assess the stage of myelination. P14 homozygous clp mice showed an a typical staining pattern of immature myelin, which resolved into a rel atively normal pattern by adulthood. Sodium channel clustering and nod e of Ranvier frequency were studied in wholemount sciatic nerves with sodium channel and MAG antibodies. P14 homozygous clp nerves again sho wed an atypical, immature pattern with diffuse sodium channel clusters suggesting nodal formation was delayed. In the adult, homozygous clp sciatic nerves displayed dramatically shortened internodal distances. The data from this study support the hypotheses that node of Ranvier f ormation begins with the onset of myelination and that the number and location of nodes of Ranvier in the sciatic nerve are determined by my elinating Schwann cells.