Trembler as a mouse model of CMT1A?
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.
Garbay
B
B
Laboratoire de Biogenèse Membranaire, UMR-CNRS 5544, Université Victor Segalen Bordeaux 2, France. Bertrand.Garbay@biomemb.u-bordeaux2.fr
Salles
J
J
Knoll
A
A
Boiron-Sargueil
F
F
Heape
A M
AM
Bonnet
J
J
Cassagne
C
C
D000818:Animals; D002607:Charcot-Marie-Tooth Disease / Q000235:genetics* / Q000473:pathology; D004195:Disease Models, Animal; D005786:Gene Expression Regulation; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D051379:Mice; D008818:Mice, Neurologic Mutants; D009185:Myelin Proteins / Q000235:genetics*; D009186:Myelin Sheath / Q000473:pathology
D009185:Myelin Proteins; C073687:PMP22 protein, human; C489545:Pmp22 protein, mouse