ANALYSIS OF a MOUSE Α-Globin GENE MUTATION INDUCED BY ETHYLNITROSOUREA

Popp, Raymond A.; Bailiff, E. G.; Skow, Loren C.; Johnson, F. M.; Lewis, Susan E.

doi:10.1093/genetics/105.1.157

Cited by 90 publications

(3 citation statements)

References 9 publications

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“…Animal studies have revealed the biological importance of A-T transversion mutations. The A-T -* T-A transversion event has been proposed to account for two mutations of the mouse a-and /5-globin genes arising in the progeny of ENUtreated female mice (Popp et al, 1983;Lewis et al, 1985).…”

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confidence: 99%

In vitro mispairing specificity of O2-ethylthymidine

Grevatt¹,

Solomon²,

Bhanot³

1992

Biochemistry

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The O2-position of thymine is a major site of base alkylation by N-nitroso-alkylating agents, and its biological relevance remains obscure. The potential significance of this DNA damage was ascertained by studying in vitro DNA replication properties of O2-ethylthymidine (O2-Et-dT) site-specifically incorporated into a 36-nucleotide template. DNA replication was initiated eight nucleotides away from the O2-Et-dT lesion by Escherichia coli polymerase I (Klenow fragment) using a 17-nucleotide primer. In the presence of 10 microM dNTP and Mg2+, O2-Et-dT blocked DNA replication predominantly (94%) 3' to O2-Et-dT, with the remainder (5%) blocked after incorporation of a nucleotide opposite O2-Et-dT (incorporation-dependent blocked product). Postlesion synthesis was negligible (less than 1%). Nucleotide incorporation opposite O2-Et-dT increased to 23% at 200 microM dNTP. Postlesion synthesis remained negligible (less than 2%). DNA sequencing revealed dA present opposite O2-Et-dT in the incorporation-dependent blocked product. Negligible postlesion synthesis suggests that incorporation of dA opposite O2-Et-dT inhibits in vitro DNA synthesis. The O2-Et-dT.dA base pair may also impede DNA synthesis in vivo, contributing to the cytotoxicity of the ethylating agents. Substitution of Mn2+ for Mg2+ enhanced nucleotide incorporation opposite O2-Et-dT and produced postlesion synthesis (16%) at 10 microM dNTP, which increased to 39% at 200 microM dNTP. DNA sequence analysis showed that while dA was present opposite O2-Et-dT in the incorporation-dependent blocked product, both dA and dT were present opposite this lesion in the postlesion synthesis product.(ABSTRACT TRUNCATED AT 250 WORDS)

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confidence: 99%

In vitro mispairing specificity of O2-ethylthymidine

Grevatt¹,

Solomon²,

Bhanot³

1992

Biochemistry

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“…By contrast, no GC to AT changes have been found induced by ENU in the mouse germ line. The only ENU-induced germ-line mutations characterized to date have been in the globin genes, and their nature has been deduced from changes in the protein sequence (POPP et al 1983;LEWIS et al 1985;PETERS et al 1985;PETERS 1986). All are AT changes; two transversions to TA and two transitions to GC.…”

Section: Discussionmentioning

confidence: 99%

The molecular basis of brown, an old mouse mutation, and of an induced revertant to wild type.

Zdárský¹,

Favor²,

Jackson³

1990

Genetics

154

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The murine b locus encodes the tyrosinase related protein, TRP-1, a putative membrane-bound, copper-containing enzyme having about 40% amino acid identity with tyrosinase. The protein is essential for production of black rather than brown hair pigment. We show that skin of mutant brown mice contains the same amount of TRP-1 mRNA as wild type. On sequencing the coding region of the mutant mRNA we find four nucleotide differences from the wild-type (Black) sequence. Two of these differences result in different amino acid residues encoded by the brown allele. By sequencing the TRP-1 gene from a mouse in which a reversion from brown to Black has been induced by ethylnitrosourea we are able to show that only one of these amino acid changes, which substitutes a tyrosine for a conserved cysteine, is the cause of the brown phenotype. This mutation is adjacent to another cysteine at which, in the analogous position in tyrosinase a mutation results in the albino phenotype. The sequence of the revertant is the first report of DNA sequence of an ethylnitrosourea-induced genetic change in mouse.

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“…This research generated numerous mutant mouse strains, but because X-rays induce double-stranded breaks (DSBs) in DNA, the approach often caused large deletions and chromosomal rearrangements that affected multiple genes, making interpretation of the mutant phenotypes difficult (Silver 1995). Radiation has been supplanted by chemical mutagenesis with the DNA alkylating agent N-ethyl-N-nitrosourea (ENU), which is more mutagenic than X-rays (Russell et al 1979) and more likely to result in point mutations (Popp et al 1983). Because screening large numbers of mice in the G3 generation is so time-and labor-intensive, there are several modified approaches that allow for recovery of recessive mutations in the G2 generation.…”

Section: Forward Genetic Screensmentioning

confidence: 99%

A most formidable arsenal: genetic technologies for building a better mouse

2020

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CARD 1757 mouse strains; 31 mESC lines Japan http://cardb.cc.kumamoto-u .ac.jp/transgenic Canadian Mouse Mutant Repository CMMR 845 mouse strains; 13,654 mESC lines Canada http://www.cmmr.ca Charles River Laboratories CRL 56 mouse strains USA https://www.criver.com Envigo (formerly Harlan Sprague Dawley) HSD 45 mouse strains USA https://www.envigo.com European Mouse Mutant Archive EMMA 6920 mouse strains. Europe https://www.infrafrontier.eu European Mouse Mutant Cell Repository EuMMCR 16,828 mESC lines. Europe http://www.eummcr.org GemPharmatech GPT 6910 mouse strains China http://www.gempharmatech .com/en MRC Harwell HAR 1491 mouse strains UK http://www.har.mrc.ac.uk JAX Mice and Services JAX 11,109 mouse strains; 2 mESC lines USA https://www.jax.org/jaxmice-and-services Korea Mouse Phenotyping Center KMPC 157 mouse strains Korea http://www.mouseinfo.kr

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ANALYSIS OF a MOUSE Α-Globin GENE MUTATION INDUCED BY ETHYLNITROSOUREA

Cited by 90 publications

References 9 publications

In vitro mispairing specificity of O2-ethylthymidine

In vitro mispairing specificity of O2-ethylthymidine

The molecular basis of brown, an old mouse mutation, and of an induced revertant to wild type.

A most formidable arsenal: genetic technologies for building a better mouse

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