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

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 scre...

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Bibliographic Details
Published in:	Genes, brain and behavior Vol. 3; no. 4; pp. 196 - 205
Main Authors:	Bacon, Y., Ooi, A., Kerr, S., Shaw‐Andrews, L., Winchester, L., Breeds, S., Tymoska‐Lalanne, Z., Clay, J., Greenfield, A. G., Nolan, P. M.
Format:	Journal Article
Language:	English
Published:	Oxford, UK; Malden, USA Munksgaard International Publishers 01-08-2004
Subjects:	Animals Chromosome Mapping Chronobiology Disorders - genetics Circadian Circadian Rhythm - genetics ENU 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 mouse Mutagenesis Mutagens mutation Phenotype phenotype‐driven screen Point Mutation
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Summary:	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.
ISSN:	1601-1848 1601-183X
DOI:	10.1111/j.1601-183X.2004.00070.x