| Abstract No.: | C-C3079 |
| Country: | Canada |
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| Title: | HNF-LP22S;TTA TRANSGENIC MICE : A NEW MODEL FOR THE STUDY OF CHARCOT MARIE TOOTH DISEASE TYPE 2. |
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| Authors/Affiliations: | 1 Florence Dequen*; 1 Jean-Pierre Julien;
1 Laval University, Québec, QC, Canada
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| Content: | Charcot Marie Tooth disease (CMT) is the most common hereditary sensory-motor neuropathy. This disease affects the peripheral nervous system. CMT can be provoked by various mutations including mutations in the neurofilament light subunit (NF-L). They lead to CMT type 2E which is the axonal form of the disease. CMT Patients suffer from walking problem but their lifespan is not affected. In particular, the NF-LP22S mutation targets the N-terminal head domain and interferes with the NF network assembly in vitro. Here, we created a double transgenic mouse with neuron specific expression of the NF-LP22S mutation which expression can be controlled by the tet-off system with administration of doxycycline. These mice are the first model with NF-L mutation for CMT2E. Doubly transgenic mice show abnormal posture of the inner limbs around 6 months of age which may lead to small locomotor deficit. The tet-off system will allow us to see if this phenotype (limb weakness) can be rescued by doxycyclin treatment and therefore elimination of the transgene expression. Furthermore, live cell imaging of axonal transport and histological analyses will give us information on how this mutation affects the NF network in the neuron cell body and the axon. This new mouse model will be a useful tool to study the role of NF in the pathology of CMT2E and perhaps lead to the discovery of new therapeutic opportunities. |
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