Novel phenotypes identified by plasma biochemical screening in the mouse.
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 (Nolan et al. 2000b). One focus of the program was the development of a blood biochemistry screen. At 8-12 weeks of age, approximately 300 ml of blood was collected from F1 offspring of ENU mutagenized male mice. This yielded approximately 125 ml of plasma, used to perform a profile of 17 standard biochemical tests on an Olympus analyzer. Cohorts of F1 mice were also aged and then retested to detect late onset phenotypes. In total, 1,961 F1s were screened. Outliers were identified by running means and standard deviations. Of 70 mice showing consistent abnormalities in plasma biochemistry, 29 were entered into inheritance testing. Of these, 9 phenotypes were confirmed as inherited, 10 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); abnormalities in bone and liver metabolism (low ALP, high ALP, high ALT, and AST); abnormal plasma electrolyte levels (high sodium and chloride); as well as phenotypes of interest for the study of diabetes (high glucose). The gene loci bearing the mutations are currently being mapped and further characterized. Our results have validated our biochemical screen, which is applicable to other mutagenesis projects, and we have produced a new set of mutants with defined metabolic phenotypes.
Hough
Tertius A
TA
MRC Mammalian Genetics Unit and UK Mouse Genome Centre, Harwell, OX11 ORD, UK. tertius@har.mrc.ac.uk
Nolan
Patrick M
PM
Tsipouri
Vicky
V
Toye
Ayo A
AA
Gray
Ian C
IC
Goldsworthy
Michelle
M
Moir
Lee
L
Cox
Roger D
RD
Clements
Sian
S
Glenister
Peter H
PH
Wood
John
J
Selley
Rachael L
RL
Strivens
Mark A
MA
Vizor
Lucie
L
McCormack
Stefan L
SL
Peters
Josephine
J
Fisher
Elizabeth M
EM
Spurr
Nigel
N
Rastan
Sohaila
S
Martin
Joanne E
JE
Brown
Steve D M
SD
Hunter
A Jacqueline
AJ
D000818:Animals; D004195:Disease Models, Animal; D005038:Ethylnitrosourea / Q000494:pharmacology; D005260:Female; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D016296:Mutagenesis; D010641:Phenotype; D010949:Plasma / Q000737:chemistry*
D005038:Ethylnitrosourea