ONION BULB CELLS IN MICE DEFICIENT FOR MYELIN GENES SHARE MOLECULAR-PROPERTIES WITH IMMATURE, DIFFERENTIATED NON-MYELINATING, AND DENERVATED SCHWANN-CELLS

Onion bulb formation is a pathological feature observed in peripheral nerves of patients suffering from inherited peripheral neuropathies su ch as Charcot-Marie-Tooth and Dejerine-Sottas diseases. An onion bulb consists of small circumferentially oriented (supernumerary) cells and their processes surrounding a large caliber axon. In the present stud y, we investigated the molecular phenotype of supernumerary cells at t he light and electron microscopic levels. The major motor (quadriceps muscle) branch of the femoral nerve from 16- to 24-month-old mice with an inactivated allele of the myelin protein. zero gene or deficient f or myelin-associated glycoprotein (MAG; PO+- and MAG(--) mice, respect ively), which have numerous onion bulbs, was teased to obtain single n erve fibers, which were then processed for immunocytochemistry. Corres ponding nerves from wild-type mice served as controls. In both PO+- an d MAG(--) mice, supernumerary cells expressed S-100, the low-affinity nerve growth factor receptor (p75, NGFr), the cell adhesion molecule L 1, the neural cell adhesion molecule (N-CAM), and glial fibrillary aci dic protein (GFAP); At the electron microscopic level, the cell surfac e of supernumerary cells was NGFr immunoreactive and L1 and N-CAM were expressed at points of contact between supernumerary cells. NGFr, L1, and N-CAM were also present in the basal lamina surrounding myelinate d axons associated with onion bulbs. Both S-100 and GFAP immunoreactiv ities were seen in the cytoplasm of supernumerary cells. In contrast, in wild-type mice myelinating Schwann cells only expressed S-100 intra cellularly and L1 and N-CAM in their basal lamina, whereas non-myelina ting Schwann cells expressed all five molecules investigated. The pres ent study indicates that supernumerary cells in onion bulbs have a mol ecular phenotype characteristic of immature, differentiated non-myelin ating, and denervated Schwann cells, thus excluding the possibility th at supernumerary cells are perineurial cells. (C) 1996 Wiley-Liss, Inc .