Given the heterogeneity of MECP2 mutations in RTT patients, to test the robustness and generalisation of CNF1 therapeutic efficacy, the present study extended the investigation to a second RTT mouse model, characterised by a more severe phenotype, carrying a MeCP2 null mutation modelling the large deletions found in 10% of RTT patients (MeCP2-Bird mice) [18]. The gene discussed is MECP2; the disease is Rett syndrome.