Readthrough of nonsense mutations in Rett syndrome: evaluation of novel aminoglycosides and generation of a new mouse model

Thirty-five percent of patients with Rett syndrome carry nonsense mutations in the MECP2 gene. We have recently shown in transfected HeLa cells that readthrough of nonsense mutations in the MECP2 gene can be achieved by treatment with gentamicin and geneticin. This study was performed to test if readthrough can also be achieved in cells endogenously expressing mutant MeCP2 and to evaluate potentially more effective readthrough compounds. A mouse model was generated carrying the R168X mutation in the MECP2 gene. Transfected HeLa cells expressing mutated MeCP2 fusion proteins and mouse ear fibroblasts isolated from the new mouse model were treated with gentamicin and the novel aminoglycosides NB30, NB54, and NB84. The localization of the readthrough product was tested by immunofluorescence. Readthrough of the R168X mutation in mouse ear fibroblasts using gentamicin was detected but at lower level than in HeLa cells. As expected, the readthrough product, full-length Mecp2 protein, was located in the nucleus. NB54 and NB84 induced readthrough more effectively than gentamicin, while NB30 was less effective. Readthrough of nonsense mutations can be achieved not only in transfected HeLa cells but also in fibroblasts of the newly generated Mecp2R168X mouse model. NB54 and NB84 were more effective than gentamicin and are therefore promising candidates for readthrough therapy in Rett syndrome patients

Estudo comparativo da capacidade de contração do assoalho pélvico em atletas de voleibol e basquetebol

As modalidades esportivas de alto impacto podem produzir um aumento exagerado e frequente na pressão intra-abdominal, um dos fatores desencadeadores da incontinência urinária de esforço (IUE) em atletas. Foi realizado um estudo com 20 atletas, sendo 10 de basquetebol e 10 de voleibol, do tipo quantitativo, observacional, transversal e comparativo, no qual foi comparada a capacidade de contração do assoalho pélvico (AP) entre atletas de voleibol e basquetebol, e então correlacionadas com sintomas de IUE. A avaliação das atletas foi composta por um questionário, a avaliação funcional do assoalho pélvico (AFA) e avaliação da capacidade de contração do AP através do Biofeedback Eletromiográfico Fênix®. Após a avaliação, não foi observada diferença estatisticamente significante com relação à capacidade de contração do assoalho pélvico entre atletas de basquetebol e voleibol; porém, ambas as modalidades apresentaram atletas com relatos de perda involuntária de urina mediante esforço físico, com maior proporção no grupo de atletas de basquetebol