Screening for ENU-Induced Mutations in Mice That Result in Aberrant Ethanol-Related Phenotypes

• Published in: Behavioral neuroscience 2007-08, Vol.121 (4), p.665-678
• Main Authors: Hamre, Kristin M, Goldowitz, Daniel, Wilkinson, Sarah, Matthews, Douglas B
• Format: Article
• Language: English
• Subjects: Alcoholic Intoxication - genetics; Alcoholic Intoxication - physiopathology; Animal; Animal Locomotion; Animal Strain Differences; Animals; Ataxia; Behavior, Animal - drug effects; Behavior, Animal - physiology; Behavioral psychophysiology; Biological and medical sciences; Drinking Behavior - drug effects; Drinking Behavior - physiology; Ethanol; Female; Fundamental and applied biological sciences. Psychology; Genetics; Genotype & phenotype; Locomotion - drug effects; Locomotion - genetics; Male; Maze Learning - drug effects; Maze Learning - physiology; Medical sciences; Mice; Mice, Inbred Strains; Motor Activity - genetics; Mutagenicity Tests - methods; Mutation; Mutation - drug effects; Mutation - physiology; Mutations; Nervous system (semeiology, syndromes); Nervous system as a whole; Neurology; Neuropharmacology; Neuropsychology; Nitrosourea Compounds - pharmacology; Pharmacology. Drug treatments; Phenotype; Phenotypes; Psycholeptics: tranquillizer, neuroleptic; Psychology. Psychoanalysis. Psychiatry; Psychology. Psychophysiology; Psychopharmacology; Rodents; Species Specificity; Time Factors
• ISSN: 0735-7044; 1939-0084
• DOI: 10.1037/0735-7044.121.4.665

One way to investigate the genetic underpinnings of ethanol-related phenotypes is to create random mutations and screen the mutagenized mice for their behavioral phenotypes. The purposes of this article are to assess the efficacy of a novel high throughput screen to detect known strain differences and to provide evidence of the ability of this screen to detect phenodeviants, as illustrated by two new lines of mutant mice. All mice were tested for the following phenotypes after a dose of 2.25 g/kg of ethanol: ataxia, anxiolytic response, locomotor activity, core body temperature, and blood ethanol concentration, as well as ethanol consumption based on a two-bottle choice test. The authors obtained several baseline measures that allowed for the detection of phenodeviants on these measures as well. To validate this screen, A/J, DBA/2J, and C57BL/6J mouse strains were tested, and previously reported strain differences were found in all phenotypes except ethanol-induced hypothermia. Additionally, two mutant pedigrees were identified: 7TNJ, which exhibited abnormal ethanol-induced locomotor activity, and 112TNR, which exhibited an enhanced ability on the rotarod. These data demonstrate the efficacy of this screen to detect known as well as novel phenotypic differences.