Type 1A CMT research news from Genova

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Research Abstract from Neurobiol Dis. 2004 Jun;16(1):263-73.

Impairment of PMP22 transgenic Schwann cells differentiation in culture:

implications for Charcot-Marie-Tooth type 1A disease.

Nobbio L, Vigo T, Abbruzzese M, Levi G, Brancolini C, Mantero S, Grandis

M, Benedetti L, Mancardi G, Schenone A.

Department of Neurosciences, Ophthalmology and Genetics, University of

Genova, 16132 Genova, Italy.

Charcot-Marie-Tooth type 1A (CMT1A) is a hereditary demyelinating

neuropathy due to an increased genetic dosage of the peripheral myelin

protein 22 (PMP22). The mechanisms leading from PMP22 overexpression to

impairment of myelination are still unclear. We evaluated expression and

processing of PMP22, viability, proliferation, migration, motility and

shaping properties, and ability of forming myelin of PMP22 transgenic

(PMP22(tg)) Schwann cells in culture. In basal conditions, PMP22(tg)

Schwann cells, although expressing higher PMP22 levels than control

ones, show normal motility, migration and shaping properties. Addition

of forskolin to the media induces an additional stimulation of PMP22

expression and results in an impairment of cells migration and motility,

and a reduction of cell area and perimeter. Similarly, co-culturing

transgenic Schwann cells with neurons causes an altered cells

differentiation and an impairment of myelin formation. In conclusion,

exposure of PMP22(tg) Schwann to the axon or to axonal-mimicking stimuli

significantly affects the transition of transgenic Schwann cells to the

myelinating phenotype.