PDF file: EURASNET Annual Report 2008

c) Main activities planned for the coming year:• Our group will further exploit the mouse SMA model mentioned above to: (i) determinethe time point when SMN production is critical and requires therapeutic boosting; (ii)study the ability of mutant SMN to counteract the SMA phenotype; (iii) study the role ofSMN in motoneurons; (iv) develop ways to deliver the therapeutic U7 transgene tomotoneurons.• Partially cured mice will be characterised in more detail to define the histologicalsituation and to compare the slower disease development to mouse models for anothermotoneuron degenerative disease, Amyotrophic lateral sclerosis (ALS).• Other work will be directed towards determining the molecular changes occurring at theglobal splicing and proteome levels in manually isolated motoneurons from SMA mice.Moreover, we will analyse the expression of candidate genes that may be important inSMA pathogenesis.• Finally, in collaboration with participant 25 (J. Stévenin,Illkirch F), we will continue tocharacterise which splicing regulator binds to the exonic splicing enhancer present in ourbifunctional U7 construct targeting exon 7 of the SMN2 gene.•164