Project description:Costello syndrome (CS) is a congenital disorder caused by heterozygous activating germline HRAS mutations in the canonical Ras/mitogen-activated protein kinase (Ras/MAPK) pathway. CS is one of the RASopathies, a large group of syndromes due to mutations within various components of the Ras/MAPK pathway. An important part of the phenotype that greatly impacts quality of life is hypotonia. To gain a better understanding of the mechanisms underlying hypotonia in CS, a mouse model with an activating HrasG12V allele was utilized. We identified a skeletal myopathy that was due in part to an inhibition of embryonic myogenesis and myofiber formation, resulting in a reduction of myofiber size and number that led to reduced muscle mass and strength. In addition to hyperactivation of the Ras/MAPK and PI3K/AKT pathways, there was a significant reduction of p38 signaling, as well as global transcriptional alterations consistent with the myopathic phenotype. Inhibition of Ras/MAPK pathway signaling using a MEK inhibitor rescued the HrasG12V myopathy phenotype both in vitro and in vivo, demonstrating that increased MAPK signaling is the main cause of the muscle phenotype in CS.
Project description:We report on gene expression in stem cell-enriched, undifferentiated spermatogonia isolated from the adult mouse testis, in which one group are wild type and the other group contain a heterozygous Hras G12V mutation.
Project description:MCF10A cells were then transfected with MEK1(S217S221), HRAS(G12V), and null control vectors Cells were lysed 24 hours post-transfection with collection of total RNA and protein Keywords: Oncogene inducation of gene expression changes
Project description:This study aimed to investigate the effects of glucose restriction (GR) on energy metabolism and muscle fiber type in skeletal muscle. To achieve this goal, we created a mouse model of innate glucose limitation by mutating the major glucose transporter 4 (Glut4) in skeletal muscle. We performed proteomic and phosphoproteomic analyzes of gastrocnemius samples from 12-week-old male Glut4m mice, with or without low-intensity treadmill training.
Project description:This study aimed to investigate the effect of glucose restriction (GR) on energy metabolism and muscle fibre type in skeletal muscle. To achieve this goal, we constructed a mouse model of innate glucose restriction by mutating the glucose transporter 4 (Glut4), the major glucose transporter in skeletal muscle. We performed proteomic and phosphoproteomic analysis on gastrocnemius samples of male Glut4m mice at 12-week age, with or without a 4-week low-intensity training.
Project description:MCF10A cells were then transfected with MEK1(S217S221), HRAS(G12V), and null control vectors; Cells were lysed 24 hours post-transfection with collection of total RNA and protein Experiment Overall Design: Overexpression of Oncogenic protein was confirmed via Western blot