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Mutations and Experimental Mutagenesis

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Genetics of the Mouse

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Abstract

The word mutation was coined in 1901 by Hugo De Vries to describe “sudden, spontaneous and drastic alterations in the hereditary material of Oenothera”, the evening primrose. Mutations occur in the genome of all living organisms and vary in importance, ranging from single base-pair changes to extensive chromosomal rearrangements. They can occur either in somatic or germ cells, at all stages of development, and are transmitted to daughter cells except when they cause death or a severe selective disadvantage.

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Notes

  1. 1.

    Hugo de Vries also used the word “sport” to define the same sort of sudden genetic changes.

  2. 2.

    Resistance to the rodenticide warfarin is a good example of the mutations that occurred in wild populations, generating a selective advantage.

  3. 3.

    Chromosomal rearrangements such as translocations of all types, transpositions, deletions, duplications, inversions, etc. have been discussed in Chap. 3 (Cytogenetics) and 5 (The Mouse Genome).

  4. 4.

    Hermann J. Muller was awarded the Nobel Prize in Physiology or Medicine for the “discovery that mutations can be induced by X-rays”.

  5. 5.

    Here we write the codon sequences as they are read on the sense (5′ to 3′) strand of DNA. In these conditions, they read the same as the RNA codons (with the exception that T is replaced by U in mRNAs). However, it must be kept in mind that the mRNA transcripts are synthesized using the antisense strand of DNA (3′ to 5′) as a template.

  6. 6.

    The average spontaneous mutation rate at the DNA level has been estimated to be 2.2 × 10−9 per nucleotide per year in the human species (Kumar and Subramanian 2002).

  7. 7.

    This is referred as nonsense-mediated mRNA decay.

  8. 8.

    Four substitutions of the first nucleobase result in a synonymous codon (lysine or arginine codons). No substitution of the second nucleobase leads to a synonymous codon.

  9. 9.

    In mouse nuclear DNA, the G + C content is 41.70 %, indicating that codons making use of these two nucleotides are under-represented in this species.

  10. 10.

    Computations of the mutation rates were made on several interstrain F1 hybrids expected to be all heterozygous for one or several of the recessive coat color alleles and the corresponding wild-type allele. In such an F1 population, the mice with a non-wild-type phenotype are potential carriers of a new mutant allele. This was confirmed by setting up separate crosses.

  11. 11.

    These observations were made on the F1 progeny of a cross between a tester stock, known as PT stock, homozygous for seven fully penetrant recessive alleles, and mice homozygous for the wild-type alleles at the same seven loci.

  12. 12.

    On a total of 36 dominant mutations.

  13. 13.

    Since 1970, the gray (Gy) has replaced the rad as a unit of absorbed radiation in terms of energy per unit of mass. One gray corresponds to one joule of energy absorbed per kilogram of living matter. One Gy is equal to 100 rads.

  14. 14.

    The publication by Arnold et al. (2012) is a rich source of information calculated on a very large sample.

  15. 15.

    The choice of the strain must be considered with care depending on the future use of the mutant potentially discovered. If mutations are induced, it will definitely be important to identify the background strain in which the mutation occurred.

  16. 16.

    The Guthrie test (a bacterial assay) was routinely used for the neonatal diagnostic of phenylketonuria. It is now replaced either by an immunoassay or by a tandem mass spectrometry assay that measures the amino acid proportions.

  17. 17.

    An increase in the plasma level of creatine phosphokinase (CPK) in these F1 mice reveals some damage to the muscular tissue, and is often an indication of the likely occurrence of a new mdx allele.

  18. 18.

    In this type of experiment it is necessary to exclusively use mice of an inbred strain to enable the non-ambiguous characterization of the mutations potentially induced in the progeny by the mutagen.

  19. 19.

    The transposons were discovered and studied in maize by Nobel laureate B. McClintock, precisely because of their mutagenic activity.

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Authors and Affiliations

  1. Institut Pasteur, Paris, France

    Jean-Louis Guénet

  2. Division of Basic Science Research, Department of Molecular Carcinogenesis, The University of Texas MD Anderson Cancer Center, Smithville, TX, USA

    Fernando Benavides

  3. Mouse Functional Genetics Unit, Institut Pasteur, Paris, France

    Jean-Jacques Panthier & Xavier Montagutelli

  4. Ecole Nationale Vétérinaire d’Alfort, Maisons-Alfort, France

    Jean-Jacques Panthier

Authors
  1. Jean-Louis Guénet
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  2. Fernando Benavides
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  3. Jean-Jacques Panthier
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  4. Xavier Montagutelli
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Correspondence to Jean-Louis Guénet .

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Guénet, JL., Benavides, F., Panthier, JJ., Montagutelli, X. (2015). Mutations and Experimental Mutagenesis. In: Genetics of the Mouse. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-662-44287-6_7

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