Implementing Large-Scale ENU Mutagenesis Screens in North America

Clark, Amander T.; Goldowitz, Dan; Takahashi, Joseph S.; Vitaterna, Martha Hotz; Siepka, Sandra M.; Peters, Luanne L.; Frankel, Wayne N.; Carlson, George A.; Rossant, Janet; Nadeau, Joseph H.; Justice, Monica J.

doi:10.1007/s10709-004-1436-6

Cited by 78 publications

(51 citation statements)

References 33 publications

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“…The resulting G1 pups can be screened directly for dominant phenotypes. Alternatively, G1 animals can be crossed again to wild type to produce multiple G2 carriers that, when backcrossed to the G1 parent or intercrossed with littermates, produce G3 progeny that can be screened for recessive phenotypes [3,4,6].…”

Section: Mutant Strain Origins: Spontaneity and Inductionmentioning

confidence: 99%

“…Nevertheless, because the genes within the inversion are still present, screening for recessive mutations requires the generation of G3 progeny, as described above. Like the deletion screen, balancer screens are also restricted to recovering mutations found within the targeted genomic region [3,4,6,10].…”

Section: Mutant Strain Origins: Spontaneity and Inductionmentioning

confidence: 99%

“…This trend was largely complemented by the publication of the mouse genome [2]; the availability of the genomic sequence facilitates mapping and mutation identification, while it was hoped that a phenotype-driven approach might be faster and more effective than knockout technology in elucidating the functions of the thousands of genes predicted from the sequence but not yet studied [3,4,5,6].…”

Section: Introductionmentioning

confidence: 99%

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Mouse Forward Genetics in the Study of the Peripheral Nervous System and Human Peripheral Neuropathy

Douglas

Popko

2008

Neurochem Res

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Forward genetics, the phenotype-driven approach to investigating gene identity and function, has a long history in mouse genetics. Random mutations in the mouse transcend bias about gene function and provide avenues towards unique discoveries. The study of the peripheral nervous system is no exception; from historical strains such as the trembler mouse, which led to the identification of PMP22 as a human disease gene causing multiple forms of peripheral neuropathy, to the more recent identification of the claw paw and sprawling mutations, forward genetics has long been a tool for probing the physiology, pathogenesis, and genetics of the PNS. Even as spontaneous and mutagenized mice continue to enable the identification of novel genes, provide allelic series for detailed functional studies, and generate models useful for clinical research, new methods, such as the piggyBac transposon, are being developed to further harness the power of forward genetics.

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Section: Mutant Strain Origins: Spontaneity and Inductionmentioning

confidence: 99%

Section: Mutant Strain Origins: Spontaneity and Inductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Mouse Forward Genetics in the Study of the Peripheral Nervous System and Human Peripheral Neuropathy

Douglas

Popko

2008

Neurochem Res

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“…These include the International Gene Trap Consortium, producing ≈190,000 gene-trapped ES cell lines, (Nord et al ., 2006 1 ), a number of N-ethyl-N-nitrosourea (ENU)-mutagenesis projects producing over 3,300 defined mutations (for example, see Andrews et al ., 2012; Boles et al , 2009; Clark et al ., 2004), and the International Knockout Mouse Consortium (IKMC) generating targeted mutations in all mouse protein-coding genes in ES cell lines, with over 14,000 genes successfully targeted to date (Bradley et al ., 2012). Genetic engineering methodologies including CRISPR/Cas (Clustered Regularly Interspaced Short Palindromic Repeats/CRISPR associated sequences) engineering (Wang et al ., 2013) and elegant, technologies that allow spatiotemporal control of gene ablation and regulation are providing new insight into gene function through the use of conditional mutagenesis (Murray et al ., 2012).…”

Section: Introductionmentioning

confidence: 99%

Mouse Genome Database: From sequence to phenotypes and disease models

Eppig

Richardson

Kadin

et al. 2015

Genesis

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The Mouse Genome Database (MGD, www.informatics.jax.org) is the international scientific database for genetic, genomic, and biological data on the laboratory mouse to support the research requirements of the biomedical community. To accomplish this goal, MGD provides broad data coverage, serves as the authoritative standard for mouse nomenclature for genes, mutants, and strains, and curates and integrates many types of data from literature and electronic sources. Among the key data sets MGD supports are: the complete catalog of mouse genes and genome features, comparative homology data for mouse and vertebrate genes, the authoritative set of Gene Ontology (GO) annotations for mouse gene functions, a comprehensive catalog of mouse mutations and their phenotypes, and a curated compendium of mouse models of human diseases. Here we describe the data acquisition process, specifics about MGD’s key data areas, methods to access and query MGD data, and outreach and user help facilities.

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“…As these reviews describe the basic methods used in forward genetic screens, including the types of screens that can be done, the sophisticated manipulations one can build into a screen to facilitate mapping, and the benefits of having a easily discernible phenotype, we will not focus on those topics (for examples, see Clark et al, 2004;Kile and Hilton, 2005;Papathanasiou and Goodnow, 2005). Here, we first illustrate how genome sequence information provides a molecular grounding for mouse forward genetics and then focus on the new aspects of biology that have been revealed in these screens.…”

Section: Introductionmentioning

confidence: 99%

Uncovering the uncharacterized and unexpected: Unbiased phenotype‐driven screens in the mouse

Caspary

Anderson

2006

Developmental Dynamics

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Phenotype-based chemical mutagenesis screens for mouse mutations have undergone a transformation in the past five years from a potential approach to a practical tool. This change has been driven by the relative ease of identifying causative mutations now that the complete genome sequence is available. These unbiased screens make it possible to identify genes, gene functions and processes that are uniquely important to mammals. In addition, because chemical mutagenesis generally induces point mutations, these alleles often uncover previously unappreciated functions of known proteins. Here we provide examples of the success stories from forward genetic screens, emphasizing the examples that illustrate the discovery of mammalian-specific processes that could not be discovered in other model organisms. As the efficiency of sequencing and mutation detection continues to improve, it is likely that forward genetic screens will provide an even more important part of the repertoire of mouse genetics in the future. Developmental Dynamics 235:2412-2423, 2006.

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Implementing Large-Scale ENU Mutagenesis Screens in North America

Cited by 78 publications

References 33 publications

Mouse Forward Genetics in the Study of the Peripheral Nervous System and Human Peripheral Neuropathy

Mouse Forward Genetics in the Study of the Peripheral Nervous System and Human Peripheral Neuropathy

Mouse Genome Database: From sequence to phenotypes and disease models

Uncovering the uncharacterized and unexpected: Unbiased phenotype‐driven screens in the mouse

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