In vivo Proliferative Pattern of Trembler Hypomyelinating Schwann Cells Is Modified in Culture: An Experimental Analysis

Abstract

Trembler mouse, a Schwann cell mutation, is characterized by severe hypomyelination of peripheral nerves, high Schwann cell proliferation and the presence of a multilayered basal lamina which surrounds them. In contrast with their continuous in vivo division, mutant Schwann cells prepared from 15-day sciatic nerves display a lower proliferation rate in cell culture than normal Schwann cells. However, quiescent Trembler Schwann cells are still able to respond, as normal Schwann cells, to exogenous mitogens, such as nerve extracts and myelin-enriched fractions. In addition, both normal and Trembler Schwann cells proliferate in response to Trembler serum. Fibroblast growth factor is not the mitogenic factor which stimulates mutant Schwann cell proliferation in vivo, since it is absent in Trembler serum and poorly concentrated in Trembler adult sciatic nerves. Our results suggest that, in vivo, the serum of Trembler mouse probably contains mitogenic factors, not yet characterized, which may trigger the permanent division of mutant Schwann cells, in contrast to the quiescent state of these cells in the nerves of normal mice.

A Patient with neurofibromatosis type 1 and Charcot–Marie–Tooth disease type 1B

“…Third, the conditional deletion of NF1 only in Schwann cells results in neurofibromas initiated by non‐myelinating Schwann cells (those associated with unmyelinated axons) 25, 26. Although Schwann cell proliferation has not been specifically measured in CMT1B, demyelination and remyelination are always, to the best of our knowledge, accompanied by Schwann cell proliferation27; this has been demonstrated for insults as varied as systemic tellurium intoxication,28 intraneural lysolecithin injection, or genetic mutation in PMP22 29–32. Although one might suspect that conditions associated with increased Schwann cell proliferation, such as CMT1,33 would result in an overwhelming disease burden, this did not appear to be the case in our patient or in the other published cases of patients with both CMT1 and NF1 17–19.…”