title: Screening for novel ENU-induced rhythm, entrainment and activity mutants.
abstract: Chemical mutagenesis has provided an opportunity to develop and expand the repertoire of behavioural mutants for gene function studies. With this in mind, we have established a screen in mice for mutations affecting circadian rhythms, entrainment to light and other wheel-running parameters. The screen consists of an assessment of mouse wheel-running activity in a 12:12 h light/dark cycle for 7-10 days followed by assessment in constant darkness for up to 20 days. Responses to light are assessed using two protocols; a 15 minute light pulse given at circadian time 16 on the tenth day in constant darkness and an additional 12 h of light upon transition from light/dark conditions to constant darkness. To date, approximately 1300 progeny of chemically mutagenised mice have been screened. Computer-aided assessment of wheel-running parameters has helped in identifying abnormal phenotypes in approximately 5% of all animals screened. Inheritance testing of mice with abnormal phenotypes has confirmed the number of robustly inherited mutant phenotypes to be 1% of the total screened. Confirmed mutants including those affecting free-running period, light-responsiveness and wheel-running endurance have been identified. Thus far, low-resolution map positions have been established for four mutants by completing genome scans in backcross progeny. Mutant loci do not correspond with those previously associated with wheel-running behaviour. This result confirms that phenotype-driven approaches such as this should continue to provide material for mammalian gene function studies.
authors.affiliation: MRC Mammalian Genetics Unit, Harwell, UK.
authors.forename: Y
authors.initials: Y
authors.lastname: Bacon
authors.forename: A
authors.initials: A
authors.lastname: Ooi
authors.forename: S
authors.initials: S
authors.lastname: Kerr
authors.forename: L
authors.initials: L
authors.lastname: Shaw-Andrews
authors.forename: L
authors.initials: L
authors.lastname: Winchester
authors.forename: S
authors.initials: S
authors.lastname: Breeds
authors.forename: Z
authors.initials: Z
authors.lastname: Tymoska-Lalanne
authors.forename: J
authors.initials: J
authors.lastname: Clay
authors.forename: A G
authors.initials: AG
authors.lastname: Greenfield
authors.forename: P M
authors.initials: PM
authors.lastname: Nolan
mesh_terms: D000818:Animals; D002874:Chromosome Mapping; D021081:Chronobiology Disorders / Q000235:genetics*; D002940:Circadian Rhythm / Q000235:genetics; D005038:Ethylnitrosourea; D005220:Fathers; D005260:Female; D030342:Genetic Diseases, Inborn / Q000235:genetics; D005820:Genetic Testing / Q000379:methods*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D008817:Mice, Mutant Strains / Q000145:classification / Q000235:genetics* / Q000502:physiology; D023421:Models, Animal; D009043:Motor Activity / Q000235:genetics*; D016296:Mutagenesis; D009153:Mutagens; D010641:Phenotype; D017354:Point Mutation
chemical_list: D009153:Mutagens; D005038:Ethylnitrosourea