Methods to rapidly and accurately screen a large number of ENU mutagenized mice for abnormal motor phenotypes.
In a dominant genetic screen for late-onset motor impairments in mice, 16-20-week-old N-nitroso-N-ethylurea (ENU)-mutagenized females were subjected to a behavioural test battery consisting of a visual assessment followed by the vertical pole, rotarod and grip strength tests. SOD1-G93A transgenic mice were tested in parallel as a positive control to provide information on the validity and sensitivity of the screen. From among the 1500 G1 ENU mice screened, four affected mice with impaired motor function were classified as outliers. Approximately 32% of the G2 and G3 progeny of one outlier were affected. Vertical pole, rotarod and grip strength test scores were significantly correlated with each other and with body weight in the G1 progeny, but the correlation with body weight was not maintained in the G2 and G3 progeny. We found that two tests, tail suspension and vertical pole, were sufficient to distinguish ENU outliers and SOD1-G93A hemizygotes from control mice, and could detect abnormalities earlier and more frequently than the other tests employed.
Abramow-Newerly
Wanda
W
Samuel Lunenfeld Research Institute, Mount Sinai Hospital, 600 University Avenue, Toronto, Ontario M5G 1X5, Canada. newerly@mshri.on.ca
Lipina
Tatiana
T
Abramow-Newerly
Maria
M
Kim
Daniel
D
Bechard
Allison R
AR
Xie
Gang
G
Clapcote
Steve J
SJ
Roder
John C
JC
D000818:Animals; D001522:Behavior, Animal / Q000502:physiology; D005038:Ethylnitrosourea / Q000633:toxicity*; D018737:Hand Strength / Q000502:physiology; D008124:Locomotion / Q000502:physiology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009043:Motor Activity / Q000502:physiology; D009069:Movement Disorders / Q000151:congenital / Q000235:genetics*; D009153:Mutagens / Q000633:toxicity*; D010641:Phenotype; D004856:Postural Balance / Q000502:physiology; D015203:Reproducibility of Results; D013482:Superoxide Dismutase / Q000235:genetics; D000072105:Superoxide Dismutase-1
D009153:Mutagens; C000606291:Sod1 protein, mouse; D013482:Superoxide Dismutase; D000072105:Superoxide Dismutase-1; D005038:Ethylnitrosourea