Screening for novel ENU-induced rhythm, entrainment and activity mutants

Genes Brain Behav. 2004 Aug;3(4):196-205. doi: 10.1111/j.1601-183X.2004.00070.x.

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.

Publication types

  • Comparative Study

MeSH terms

  • Animals
  • Chromosome Mapping
  • Chronobiology Disorders / genetics*
  • Circadian Rhythm / genetics
  • Ethylnitrosourea
  • Fathers
  • Female
  • Genetic Diseases, Inborn / genetics
  • Genetic Testing / methods*
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C3H
  • Mice, Mutant Strains / classification
  • Mice, Mutant Strains / genetics*
  • Mice, Mutant Strains / physiology
  • Models, Animal
  • Motor Activity / genetics*
  • Mutagenesis
  • Mutagens
  • Phenotype
  • Point Mutation*

Substances

  • Mutagens
  • Ethylnitrosourea