The induction of recessive mutations in mouse primordial germ cells with N-ethyl-N-nitrosourea

Shibuya, Tohru; Murota, Tetsuro; Horiya, N.; Matsuda, Hiroshi; Hara, Takumi

doi:10.1016/0027-5107(93)90168-f

Cited by 24 publications

(13 citation statements)

References 16 publications

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“…Taken together, it seems that heritable damage was induced in embryonic germ cells (i.e., PGCs) after exposure to EB or EE, and the oŠspring inherited the damage and were sensitized to spontaneous teratogenesis. PGCs are at risk of chemical induction of transmissible changes, as shown by the induction of speciˆc-locus mutations and dominant skeletal mutations with ENU (12,14). However, it is not clear whether the germ-cell damage responsible for the eŠects observed in our transgenerational teratogenic studies with synthetic estrogens was genetic or``epigenetic'' in nature.…”

Section: Transgenerational Adverse Events Induced By Endocrine Disrupmentioning

confidence: 59%

“…With the treatment schedule used in our study, primordial germ cells (PGCs) were exposed to estrogenic drugs. Critical evidence for the susceptibility of mouse PGCs to genetic damage was reported by Shibuya and co-workers (12,13). They treated transplacentally C3H/He mice with varying doses of ethylnitrosourea (ENU) on gestational day 8.5, 10.5 or 13.5 and examined the incidence of recessive visible mutations at six speciˆc-loci in F1 of a cross of the treated males×tester females from the PW strain.…”

Section: Introductionmentioning

confidence: 99%

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Transgenerational Teratogenesis by Prenatal Exposure to Endocrine Disrupting Chemicals

Nagao

Takada

Onoda

2011

Genes and Environment

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Section: Transgenerational Adverse Events Induced By Endocrine Disrupmentioning

confidence: 59%

Section: Introductionmentioning

confidence: 99%

Transgenerational Teratogenesis by Prenatal Exposure to Endocrine Disrupting Chemicals

Nagao

Takada

Onoda

2011

Genes and Environment

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“…After administration of ENU through intraperitoneal injection to adult male mice, mutations are induced by transfer of an ethyl group to any of a number of sites on each of the four deoxyribonucleotides [1]. The dosage and number of injections of ENU are critical as too much will affect both the viability and long-term fertility of the mice [2,3], whereas too little allows repair of mutations by normal cellular DNA repair mechanisms [4,5]. One of the major sites for ENU action in the mouse is spermatogonial stem cells, thus enabling mutations to be transmitted to the next generation [6,7].…”

Section: Using Enu (N-ethyl-n-nitrosourea) To Induce Mutations In Micementioning

confidence: 99%

ENU mutagenesis as a tool for understanding lung development and disease

Yates

McMurray

Zhang³

et al. 2009

Biochemical Society Transactions

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ENU (N-ethyl-N-nitrosourea) is a chemical mutagen that randomly induces point mutations in DNA. Since the 1990s ENU has been successfully used as a means to obtain mouse mutants using both gene-driven (reverse genetics) and phenotype-driven (forward genetics) approaches. A high-efficiency ENU approach results in approx. 25 functional mutations per genome; most of these will result in hypomorphic alleles. Our group has recently begun using ENU mutagenesis as a tool for understanding lung development and disease. In collaboration with other groups at MRC Harwell, we have undertaken a screen for recessive mutations affecting mouse lung development. We are currently pursuing two lines identified from this screen, Hel (head, eye and lung) and RecBA17. Both these lines exhibit lung defects and we believe that by studying the phenotypes and identifying the causative mutations, we may also shed light on lung disease pathogenesis. In collaboration with Bill Cookson and Miriam Moffatt, we are also taking a gene-driven approach for understanding asthma. Using the Harwell ENU sperm archive, we have recovered mouse lines harbouring mutations in the asthma-susceptibility genes Phf11 (PHD finger protein 11) and Dpp10 (dipeptidylpeptidase 10). Functional analyses of these alleles are currently under way.

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“…Direct evidence is available for mutation induction in germ cells of the developing embryo and subsequent transmission to offspring. Several studies report that the germ cell mutation rate is increased in mouse embryos treated at 8-13 days of gestation [Shibuya et al, 1993;Russell et al, 19901. Although the data are limited, they suggest that male germ cells in the embryo may be more sensitive to mutagenic agents than in the adult.…”

Section: Mosaicism In Experimental Organismsmentioning

confidence: 99%

Mosaicism: The embryo as a target for induction of mutations leading to cancer and genetic disease

Mohrenweiser

Zingg

1995

Environ. Mol. Mutagen.

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Mosaicism, the existence of "patches" of cells with a genetic constitution that differs from that of other cells of an organism, has been observed in both germinal and somatic tissues of several species, including humans. Mutational events occurring during early embryogenesis can give rise to an organism with a significant number of cells with the mutant genotype in one or more tissues. If this event occurs in a precursor of the germ cells, the mutation can be transferred to subsequent generations. In the F1 generation, this event will usually be perceived as a de novo germinal mutation rather than a transmitted variant allele, unless significant effort is directed toward detecting the mosaicism. Similarly, mutations in oncogenes and tumor-suppressor genes in proliferating somatic cells can generate populations of cells that are at increased risk of transforming into tumor cells. The number of potential preneoplastic cells is larger when the mutagenic event occurs in early development than if it occurs in the mature adult. Experimental data confirm that treatment of the developing embryo or fetus with carcinogenic and mutagenic agents increases the cancer incidence in these animals and the frequency of mutations in the offspring of the animals that were exposed in utero. The available data are conclusive that the developing organism is at risk from exposure to mutagenic and carcinogenic agents. However, the data are insufficient to estimate the level of risk associated with exposures in utero, relative to either the background (spontaneous) level of risk or risk associated with similar exposures to the adult organism.(ABSTRACT TRUNCATED AT 250 WORDS)

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The induction of recessive mutations in mouse primordial germ cells with N-ethyl-N-nitrosourea

Cited by 24 publications

References 16 publications

Transgenerational Teratogenesis by Prenatal Exposure to Endocrine Disrupting Chemicals

Transgenerational Teratogenesis by Prenatal Exposure to Endocrine Disrupting Chemicals

ENU mutagenesis as a tool for understanding lung development and disease

Mosaicism: The embryo as a target for induction of mutations leading to cancer and genetic disease

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