International Mammalian Genome Society

The 16th International Mouse Genome Conference (2002)


POSTER 151 - MOUSE MODELS OF HUMAN METABOLIC DISORDERS - CHARACTERISATION OF MUTANT LINES WITH ABNORMAL LEVELS OF PLASMA ALKALINE PHOSPHATASE

T. Hough
Medical Research Council

1) Nolan P, 2) Tsipouri V, 1) Vizor L, 1) Cox RD, 2) Gray I, 1) Peters J, 2) Spurr N, 2) Rastan S, 3) Martin J, 4) Fisher E, 2) Hunter AJ, 3) Brown SDM
1) MRC, 2) GlaxoSmithKline, 3) Queen Mary School of Medicine and Dentistry 4) Institute of Neurology

The Harwell ENU mutagenesis programme aims to generate novel mouse mutants and investigate the mutations responsible for their specific phenotypes. One focus of the programme was a blood biochemistry screen. Around the ages of 8-14 weeks a blood sample was collected from the F1 offspring of mutagenised BALB/c male mice crossed to C3H females. 125ml of plasma was used to perform a profile of 17 standard biochemical tests on an Olympus analyser. In total 1,961 F1s were screened. Outliers were identified using running means and standard deviations. Of 70 mice showing consistent abnormalities in plasma biochemistry, 43 were entered into inheritance testing. Of these, 15 phenotypes were confirmed as inherited, 21 found not to be inherited and 7 are still being tested. Two of the lines for which inheritance has been confirmed, GENA 328 and GENA 381 respectively display significantly lowered and elevated levels of plasma alkaline phosphatase (ALP). GENA 328 (low ALP) is of particular interest for the study of the human condition hypophosphatasia and maps to chromosome 4. A point mutation in the candidate gene Akp2 has been found using DHPLC. Investigation of the effect of this mutation is underway. GENA 381 (high ALP) is of potential interest for the study of hyperparathyroidism and a variety of bone disorders the locus bearing the cuasative mutation is currently being mapped. Both lines are also being subjected to extensive phenotypic analysis and may offer valuable contributions to the mouse phenome database and the study of human metabolic disorders.


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