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MOUSE PHENOME PROJECT

Observer-rated ataxia: rating scales for assessment of genetic differences in ethanol-induced intoxication in mice

¹Portland Alcohol Research Center, Department of Veterans Affairs Medical Center, and Department of Behavioral Neuroscience, Oregon Health & Science University, Portland, Oregon 97239; and ²Great Lakes Institute for Environmental Research, University of Windsor, Windsor, Ontario, Canada N9B 3P4

Submitted 27 January 2004 ; accepted in final form 15 March 2004

Identification of genetic and physiological mechanisms underlying a drug's or mutation's effects on motor performance could be aided by the existence of a simple observation-based rating scale of ataxia for mice. Rating scales were developed to assess ataxia after ethanol (2.75, 3.0, and 3.25 g/kg) in nine inbred mouse strains. Each scale independently rates a single behavior. Raters, blinded to dose, scored four behaviors (splay of hind legs, wobbling, nose down, and belly drag) at each of four time points after injection. The severities of hind leg splaying and wobbling were quantifiable, whereas nose down and belly dragging were expressed in all-or-none fashion. Interrater reliabilities were substantial (0.75 r 0.99). Splay scores (rated 0–5) displayed significant effects of strain, dose, and time point. Wobbling (rated 0–4) was dependent on strain and time point. Ethanol affected wobbling (most strains scored >0 at some time), but all doses were equally effective. Incidence of nose down and belly dragging behaviors increased strain dependently after ethanol, but strains did not differentially respond to dose. Ethanol-induced splaying was modestly, and negatively, genetically correlated with wobbling. Nose down and belly dragging tended to be associated with splaying and wobbling at later times. Four distinct ataxia-related behaviors were sensitive to ethanol. Strains differed in ethanol sensitivity for all measures. Modest strain mean correlations among behaviors indicate that these behaviors are probably under control of largely different genes and that ataxia rating scales should rate separate behaviors on discrete scales.

inbred strains; mouse; pharmacogenetics; gait; coordination

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