BioProject

The present research is devoted to the identification of gene(s) severely affected by LMNA mutations, leading to striated muscle laminopathies and more specifically the cardiomyopathy. More...

The present research is devoted to the identification of gene(s) severely affected by LMNA mutations, leading to striated muscle laminopathies and more specifically the cardiomyopathy. For this purpose, we developped a large-scale gene expression approach on heart and skeletal tissues from Lmna H222P heterozygous Knock-In mouse model. Keywords: disease state modification Overall design: In the project presented here we performed differential expression in heart from a mouse model of EDMD: a LmnaH222P knock-in mouse created via homologous recombination by Gisele Bonne in Paris, France (Arimura et al., 2005). The mutant male LmnaH222P knock-in homozygous mice display reduced locomotion activity with abnormal stiff walking posture and all of them die by 9 months of age. As for cardiac phenotype, they develop chamber dilation and hypokinesia with conduction defects. These results demonstrate that LmnaH222P knock-in homozygous mice represents a good model for studying laminopathies affecting striated muscles as they develop a dystrophic condition of both skeletal and cardiac muscles reminiscent of the human diseases. Genes were identified as differentially expressed if they met a false discovery rate threshold of 0.05 in a two-sample t-test (q-value) and showed at least a two-fold difference in expression independent of absolute signal intensity. Less...