N-Ethyl-N-nitrosourea-induced prenatally lethal mutations define at least two complementation groups within the embryonic ectoderm development (eed) locus in mouse Chromosome 7

Rinchik, Eugene M.; Carpenter, Donald A.

doi:10.1007/bf00360583

Cited by 39 publications

(21 citation statements)

References 14 publications

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“…The fine deletion mapping of ENU-induced mutations, such as that performed here and for Tyr-region mutations previously ascertained in a similar type of hemizygosity screen (14,31,37), provides a robust way of placing presumed point mutations defined solely by aberrant phenotype into evolving DNA sequence and transcription maps. Indeed, even if recessive mutations are initially recovered by other strategies (such as inversion-based regional homozygosity screens or whole-genome recessive-mutation screens) (8,9,13,17), deletion mapping can be an important tool for correlating point-mutation maps with sequence maps.…”

Section: Discussionmentioning

confidence: 98%

Functional annotation of mammalian genomic DNA sequence by chemical mutagenesis: A fine-structure genetic mutation map of a 1- to 2-cM segment of mouse chromosome 7 corresponding to human chromosome 11p14-p15

Rinchik

Carpenter

Johnson

2002

Proc. Natl. Acad. Sci. U.S.A.

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Eleven independent, recessive, N-ethyl-N-nitrosourea-induced mutations that map to a Ϸ1-to 2-cM region of mouse chromosome (Chr) 7 homologous to human Chr 11p14-p15 were recovered from a screen of 1,218 gametes. These mutations were initially identified in a hemizygous state opposite a large p-locus deletion and subsequently were mapped to finer genomic intervals by crosses to a panel of smaller p deletions. The 11 mutations also were classified into seven complementation groups by pairwise crosses. Four complementation groups were defined by seven prenatally lethal mutations, including a group (l7R3) comprised of two alleles of obvious differing severity. Two allelic mutations (at the psrt locus) result in a severe seizure and runting syndrome, but one mutation (at the fit2 locus) results in a more benign runting phenotype. This experiment has added seven loci, defined by phenotypes of presumed point mutations, to the genetic map of a small (1-2 cM) region of mouse Chr 7 and will facilitate the task of functional annotation of DNA sequence and transcription maps both in the mouse and the corresponding human 11p14-p15 homology region.N-ethyl-N-nitrosourea ͉ regional mutagenesis ͉ allelic series ͉ seizures and runting ͉ prenatal and juvenile abnormalities T he supermutagenicity of N-ethyl-N-nitrosourea (ENU) (1) has made it possible to recover heritable mutations at high frequency from mouse spermatogonial stem cells. Consequently, it is possible to use phenotype-driven strategies to recover new ENU-induced mutations in specific, preselected loci for the generation of new alleles (1-4), in whole-genome screens for genes comprising components of complex pathways or phenotypes (5-10), or, with the use of chromosomal rearrangements, in a wide variety of genes within specific chromosomal regions (11-18). The phenotyping protocols used in such strategies can range from simple to complex and can be narrowly or broadly focused, with the output of any experiment dependent largely on the discriminating power of the phenotyping used. The extensive homologies between the genomes of mouse and human make it feasible to use the mouse for discovery of new mutations and phenotypes that aid in the functional annotation of the corresponding human DNA sequence and transcription maps.The region of mouse chromosome (Chr) 7 surrounding the pink-eyed dilution (p) locus that shares homology with human genomic regions 15q11-q13 and 11p14-p15 is being characterized by both genetic and molecular approaches (15,(19)(20)(21)(22)(23)(24)(25)(26). We previously reported initial results of a hemizygosity-screen strategy for recovering ENU-induced recessive mutations within the 4-to 5-cM Del(ru2 p) 46DFiOD deletion (15); this strategy is similar to a mutation-recovery experiment carried out for a 6-to 11-cM deletion at the more distally mapping Chr 7 tyrosinase [Tyr; previously, albino (c)] locus (14,16). The initial phase of this ''p-region screen'' (like the entire Tyr-region screen) used simple phenotyping criteria such as recognizing lethal...

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Section: Discussionmentioning

confidence: 98%

Functional annotation of mammalian genomic DNA sequence by chemical mutagenesis: A fine-structure genetic mutation map of a 1- to 2-cM segment of mouse chromosome 7 corresponding to human chromosome 11p14-p15

Rinchik

Carpenter

Johnson

2002

Proc. Natl. Acad. Sci. U.S.A.

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“…In this scheme, coat color alleles of various severity for albino (c) or pink-eyed dilute (p) were used to distinguish between chromosomes contributed by different parents and, thus, to allow identification of progeny carrying new mutations in the interval of interest (43,46). In this manner, embryonic lethal, developmental mutations, such as eed and fit-1, were first recovered (39,44). In the example shown in Fig.…”

Section: Chromosome Engineering and Region-specific Screensmentioning

confidence: 99%

N -Ethyl- N -Nitrosourea Mutagenesis: Boarding the Mouse Mutant Express

Cordes

2005

Microbiol Mol Biol Rev

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In the mouse, random mutagenesis with N-ethyl-N-nitrosourea (ENU) has been used since the 1970s in forward mutagenesis screens. However, only in the last decade has ENU mutagenesis been harnessed to generate a myriad of new mouse mutations in large-scale genetic screens and focused, smaller efforts. The development of additional genetic tools, such as balancer chromosomes, refinements in genetic mapping strategies, and evolution of specialized assays, has allowed these screens to achieve new levels of sophistication. The impressive productivity of these screens has led to a deluge of mouse mutants that wait to be harnessed. Here the basic large- and small-scale strategies are described, as are the basics of screen design. Finally, and importantly, this review describes the mechanisms by which such mutants may be accessed now and in the future. Thus, this review should serve both as an overview of the power of forward mutagenesis in the mouse and as a resource for those interested in developing their own screens, adding onto existing efforts, or obtaining specific mouse mutants that have already been generated

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“…The 17Rn5 1989SB and 17Rn5 3354SB mice in this study were generated from regional mutagenesis experiments as previously described (Rinchik and Carpenter, 1993;Rinchik et al, 1990 …”

Section: Micementioning

confidence: 99%

The Polycomb-group gene eed regulates thymocyte differentiation and suppresses the development of carcinogen-induced T-cell lymphomas

et al. 2002

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The mouse Polycomb-group gene, embryonic ectoderm development (eed), appears to regulate cellular growth and dierentiation in a developmental and tissue speci®c manner. During embryogenesis, eed regulates axial patterning, whereas in the adult eed represses proliferation of myeloid and B cell precursors. The present report demonstrates two novel functional activities of eed: alteration of thymocyte maturation and suppression of thymic lymphoma development. Mice that inherit the viable hypomorphic 17Rn5 CD25+ stage of thymocyte dierentiation. Furthermore, mice that are homozygous or heterozygous for the hypomorphic eed allele have an increased incidence and decreased latency of N-methyl-N-nitrosourea-induced thymic lymphoma compared to wild-type littermates. These ®ndings support the notion that Polycomb-group genes exert pleiotrophic eects dictated by developmental stage and cellular context.

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N-Ethyl-N-nitrosourea-induced prenatally lethal mutations define at least two complementation groups within the embryonic ectoderm development (eed) locus in mouse Chromosome 7

Cited by 39 publications

References 14 publications

Functional annotation of mammalian genomic DNA sequence by chemical mutagenesis: A fine-structure genetic mutation map of a 1- to 2-cM segment of mouse chromosome 7 corresponding to human chromosome 11p14-p15

Functional annotation of mammalian genomic DNA sequence by chemical mutagenesis: A fine-structure genetic mutation map of a 1- to 2-cM segment of mouse chromosome 7 corresponding to human chromosome 11p14-p15

N -Ethyl- N -Nitrosourea Mutagenesis: Boarding the Mouse Mutant Express

The Polycomb-group gene eed regulates thymocyte differentiation and suppresses the development of carcinogen-induced T-cell lymphomas

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