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Capitalizing on large-scale mouse mutagenesis screens

Nature Reviews Genetics volume 1, pages 109–115 (2000)Cite this article

Variation is the crux of genetics. Mutagenesis screens in organisms from bacteria to fish have provided a battery of mutants that define protein functions within complex pathways. Large-scale mutation isolation has been carried out in Caenorhabditis elegans, Drosophila melanogaster and zebrafish, and has been recently reported in the mouse in two screens that have generated many new, clinically relevant mutations to reveal the power of phenotype-driven screens in a mammal.

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Figure 1: Dominant screens to isolate new human disease models.
Figure 2: A three-generation breeding scheme without genetic markers to isolate recessive mutations.
Figure 3: A mouse balancer chromosome.
Figure 4: Isolating recessive detrimental mutations with a marked balancer chromosome.

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Acknowledgements

The author thanks H. Bellen for the critical reading of this manuscript and for sharing his knowledge of the history and current status of Drosophila melanogaster genetics, and Andrew Sallinger for photographing the mice in Fig. 3. This work was supported by a United States Public Health Service grant.

Author information

Authors and Affiliations

  1. Department of Molecular and Human Genetics, Baylor College of Medicine, 1 Baylor Plaza, Houston, 77030, Texas, USA

    Monica J. Justice

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  1. Monica J. Justice
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DATABASE LINKS

Kit

Kitl

Whl

ank

Wnt3

FURTHER INFORMATION

UK ENU Mutagenesis programme

German ENU-mouse mutagenesis screen project

Drosophila stock centre

Mouse Genomics and Genetics Resources Committee

Australia

Canadian mutagenesis centre

Chris Goodnow at Australian National University

Baylor mouse genome project

The gene ontology project

Mouse Genome Database (MGD)

Glossary

GENE TRAPPING

A mutation strategy that uses insertion vectors to trap or isolate transcripts from flanking genes. The inserted sequence acts as a tag from which to clone the mutated gene.

ALLELIC SERIES

An array of possible mutant forms of a gene, which usually cause multiple phenotypes.

HYPOMORPH

A mutant allele that does not eliminate the wild-type function of a gene and may give a less severe phenotype than a loss-of-function mutant.

COMPLEMENTATION

When two mutations are combined in an organism and the phenotype is wild type, the mutations are said to complement each other.

ANTIMORPH

A mutant allele that antagonizes gene function and acts in a semi-dominant manner.

MISSENSE MUTATION

A mutation that results in the substitution of an amino acid in a protein.

NONSENSE MUTATION

A mutation that results in the introduction of a stop codon to cause the premature termination of the protein.

HAPLOINSUFFICIENT

A phenotype that arises in diploid organisms owing to the loss of one functional copy of a gene.

ELISA (ENZYME-LINKED IMMUNOSORBENT ASSAY.)

A sensitive antibody-based method for the detection of an antigen such as a protein.

BACKCROSS

The mating of an individual with its parent, or with an individual of the same genotype as its parent, to follow the inheritance of alleles and phenotypes.

DNA POOLING

A mapping strategy that pools DNA from phenotypically distinct backcross or intercross progeny to identify marker alleles that are linked to the genes that determine phenotype; it reduces the time and expense of genotyping individual mice from linkage crosses.

FORWARD GENETICS

A genetic analysis that proceeds from phenotype to genotype by positional cloning or candidate-gene analysis.

REVERSE GENETICS

A genetic analysis that proceeds from genotype to phenotype by gene-manipulation techniques, such as homologous recombination in ES cells.

PARTHENOGENESIS

The production of offspring by a female with no genetic contribution from a male.

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Justice, M. Capitalizing on large-scale mouse mutagenesis screens. Nat Rev Genet 1, 109–115 (2000). https://doi.org/10.1038/35038549

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