paper questions Flashcards
what causes Charcot Marie tooth disease?
A duplication in PM22 gene which causes a reduction in myelin within Schwann cells
what is a key feature of CMT1A?
secondary axon death
what was the general background/ premise to the paper?
c-jun has been shown to be activated within injured peripheral nerves. It governs the transformation into a repair cell. It has been shown to be upregulated in response to cut and crush injuries but also in human biopsies of the disease CMT. So, does it act to prevent neuronal death within CMT?
what did the paper generally do?
they compared the phenotypes of C3 mouse model to C3, conditional c-jun KO. The conditional KO was carried out using a P0 promoter. use homologue recombination to FLP out the cre.
what were the functional assays they observed during the comparison?
- they confirmed that the c-jun levels were raised in diseased model using western blot and immunolabelling.
- they used sensory motor testing to show that C3 mouse underperformed.
- the mice showed reduced hat sensitivity and touch sensation.
- there was reduced conduction velocity within motor neurones in C3 mice.
- they observed dysmyelination of the sensory and motor axons.
what were the results of the comparisons of the functional assays of the diseased and diseased+c-jun null .
- C3 mice expressing c-jun consistently outperformed C3 in every test of sensory motor performance.
- they saw significant loss of myelin competent axons, which was more extensive in the distal nerves.
- shortening in F wave (suggesting impairment of the function of spinal cord motor neurons).
what is an F-wave?
you measure it by stimulating the skin surface, the orthodromic impulse stimulates the muscle contraction. When the antidromic impulse reaches the motor neuron cell bodies, a small portion of motor neurons backfire and orthodromic waves travels back down the nerve towards the muscle. This causes the F -wave which is smaller than the M wave.
what would you do not after this paper?
- c-jun is a transcription factor: tissue specific transcriptional profiling of what genes it is binding to in the disease response of both injury and disease.
- is this being activated autonomously as a result of PM22 or is it signals from the axon (can you culture a diseased neuron in vitro with a normal schwann cell and it still respond and vice versa)?
