Implementation of a large-scale ENU mutagenesis program: towards increasing the mouse mutant resource (original) (raw)

Abstract.

Systematic approaches to mouse mutagenesis will be vital for future studies of gene function. We have begun a major ENU mutagenesis program incorporating a large genome-wide screen for dominant mutations. Progeny of ENU-mutagenized mice are screened for visible defects at birth and weaning, and at 5 weeks of age by using a systematic and semi-quantitative screening protocol—SHIRPA. Following this, mice are screened for abnormal locomotor activity and for deficits in prepulse inhibition of the acoustic startle response. Moreover, in the primary screen, blood is collected from mice and subjected to a comprehensive clinical biochemical analysis. Subsequently, secondary and tertiary screens of increasing complexity can be used on animals demonstrating deficits in the primary screen. Frozen sperm is archived from all the male mice passing through the screen. In addition, tail tips are stored for DNA. Overall, the program will provide an extensive new resource of mutant and phenotype data to the mouse and human genetics communities at large. The challenge now is to employ the expanding mouse mutant resource to improve the mutant map of the mouse. An improved mutant map of the mouse will be an important asset in exploiting the growing gene map of the mouse and assisting with the identification of genes underlying novel mutations—with consequent benefits for the analysis of gene function and the identification of novel pathways.

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Authors and Affiliations

1. MRC Mammalian Genetics Unit and UK Mouse Genome Centre, Harwell, UK, GB
   Patrick M. Nolan, Jo Peters, Lucie Vizor, Mark Strivens, Rebecca Washbourne, Tertius Hough, Christine Wells, Peter Glenister, Claire Thornton & Steve D.M. Brown
2. Department of Morbid Anatomy, Queen Mary and Westfield College, London, UK, GB
   Jo Martin
3. Neurogenetics Department, Imperial College, London, UK, GB
   Elizabeth Fisher
4. SmithKline Beecham Pharmaceuticals, New Frontiers Science Park, Harlow, UK, GB
   Derek Rogers, Jim Hagan, Charlie Reavill, Ian Gray, John Wood, Nigel Spurr, Mick Browne, Sohaila Rastan & Jackie Hunter

Authors

1. Patrick M. Nolan
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2. Jo Peters
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3. Lucie Vizor
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4. Mark Strivens
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5. Rebecca Washbourne
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6. Tertius Hough
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7. Christine Wells
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8. Peter Glenister
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9. Claire Thornton
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10. Jo Martin
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11. Elizabeth Fisher
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12. Derek Rogers
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13. Jim Hagan
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14. Charlie Reavill
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15. Ian Gray
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16. John Wood
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17. Nigel Spurr
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18. Mick Browne
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19. Sohaila Rastan
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20. Jackie Hunter
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21. Steve D.M. Brown
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Received: 16 December 1999 / Accepted: 16 December 1999

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Nolan, P., Peters, J., Vizor, L. et al. Implementation of a large-scale ENU mutagenesis program: towards increasing the mouse mutant resource.Mammalian Genome 11, 500–506 (2000). https://doi.org/10.1007/s003350010096

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• Published: 25 February 2014
• Issue Date: July 2000
• DOI: https://doi.org/10.1007/s003350010096