Metabolic Aging Screen
We have begun a screen for metabolic disease traits in recessive G3 ENU pedigrees. In particular we are interested in diabetes traits and diabetic complications.
ENU mutagenesis followed by metabolic phenotyping of pedigrees generated as part of the Harwell Ageing Mutant screen will lead to the identification of new genes involved in the pathogenesis of type 2 diabetes and complications in aged mice. Cohorts of approx 50 G3 males are studied between 3 and 18 months of age with multiple testing to follow phenotype parameters over age. Body composition is assessed at 3, 6 12 and 18 months of age by Echo-MRI analysis. A fasted metabolic blood biochemistry profile including insulin, glucose, frucosamine, kidney function (Creatinine), liver function (ALP, ALT), Cholesterol (total and H-DL) plus a lipid profile (Triglycerides, glycerol free fatty acids) at 5, 8, 14 and 18 months of age. Cohorts with individuals with elevated plasma glucose and insulin have additional Intra-Peritoneal Glucose tolerance tests (IPGTT) performed at 4, 7, 13 and 18 months of age. Outliers (more than 2 SD from population mean) are identified as affected, the design of the screen allowing for the identification of both dominant and recessive mutations.
Pedigrees with traits undergo SNP mapping and next generation sequencing in order to identify the underlying gene.