International Mammalian Genome Society

The 15th International Mouse Genome Conference (2001)


Mr. Tertius Hough
Medical Research Council
UK Mouse Genome Centre
Harwell, Didcot
Oxfordshire, OX11 0RD

Co-Authors: 1)Hunter AJ, 2)Nolan PM, 2)Peters J, 3)Fisher EMC, 1)Gray IC, 1)Tsipouri V, 1)Rastan S, 4)Martin J, 2)Vizor L, 1)Spurr NK, 2)Moir L, 2)Toye A, 2)Goldsworthy M, 2)Cox R, 2)Brown SDM
Institutions: 1)Glaxo SmithKline Pharmaceuticals, 2)MRC Mammalian Genetics Unit and Mouse Genome Centre, 3)Department of Neurogenetics, Imperial College, 4)Department of Morbid Anatomy, Queen Mary and Westfield College

We used ENU mutagenesis in the mouse for the rapid generation of novel mutant phenotypes for both gene function studies and use as new animal models of human disease.  One focus of the programme was a blood biochemistry screen.  At 8 - 12 weeks of age around 300 ml of blood was collected from F1 offspring of ENU mutagenised males.  This yielded approximately 125 ml of plasma used to perform a profile of 17 standard biochemical tests on an Olympus analyser.  Male and female data were analysed separately.  Outliers were identified using running means and SD's.  Cohorts of F1 mice were also aged and then retested to detect late onset phenotypes.

Over 2000 F1's were screened.  29 mice showing consistent abnormalities in plasma biochemistry were entered into inheritance testing.  Of these, 10 lines were confirmed as inherited, 9 found not to be inherited and 10 are still being tested.  Inherited mutant phenotypes include abnormal lipid profiles (low total- and HDL cholesterol, high triglycerides), diabetic conditions (high glucose), abnormal bone and liver function (low ALP, high ALP, high ALT and AST) and abnormal plasma electrolyte levels (high sodium and chloride).  These mutants are currently being mapped and further characterised.  Our results have shown that incorporation of a biochemical screen is useful in detecting and characterising novel mutant phenotypes.

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