Abstract:
The Trembler mouse suffers from a dominantly inherited autosomal mutation
that results in an abnormal myelination of the peripheral
nervous system. Biochemical studies have shown that dysmyelination
is the primary event, demyelination being a late-occurring
process. The expression of myelin protein genes has been studied. The
steady-state levels for PMP22 mRNA represent 10 and 5%
of normal values in the nerves of heterozygous and homozygous Trembler,
respectively, This is due to a reduced expression of the
specific transcript driven by the promoter 1 of the PMP22 gene. Collective
results indicate that Trembler dysmyelination is not
necessarily the consequence of a large accumulation of the mutated
PMP22 protein, Moreover, it appears that the situation in the
Trembler is different from that encountered in most CMT1A patients,
where an increased PMP22 gene dosage is responsible for the
disease. Therefore, the Trembler mutant is perhaps not an ideal model
for this human neuropathy.