Journal
AMYOTROPHIC LATERAL SCLEROSIS
Volume 7, Issue 2, Pages 112-118Publisher
INFORMA HEALTHCARE
DOI: 10.1080/14660820500443000
Keywords
ENU mutagenesis; mice; motor impairment; SOD1-G93A
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Funding
- NINDS NIH HHS [R21 NS 41655-01A1] Funding Source: Medline
- NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE [R21NS041655] Funding Source: NIH RePORTER
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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 G(1) ENU mice screened, four affected mice with impaired motor function were classified as outliers. Approximately 32% of the G(2) and G(3) 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 G(1) progeny, but the correlation with body weight was not maintained in the G(2) and G(3) 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.
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