[28] Gene transfer into mouse embryos: Production of transgenic mice by pronuclear injection

Gordon, Jon W.; Ruddle, Frank H.

doi:10.1016/0076-6879(83)01031-9

Cited by 206 publications

(78 citation statements)

References 7 publications

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“…Transgenic mice may be created 'classically' through (1) direct pro-nuclear injection of exogenous DNA into fertilized zygotes (Gordon and Ruddle, 1983;Brinster et al, 1985;Palmiter and Brinster, 1986), implantation into a pseudo-pregnant female-generating transgenic progeny or (2) via injection of genetically modified mouse embryonic stem (ES) cells into a blastocyst (Doetschman et al, 1985;Gossler et al, 1986;Robertson et al, 1986) (embryonic day 4.5) with (3) embryonic retroviral infection (Jaenisch, 1980;Jaenisch et al, 1981;Soriano and Jaenisch, 1986), representing a further alternative. While direct pronuclear injection of exogenous DNA results in indiscriminate integration into the genome and is reliant upon overexpression of the transgene to generate a phenotype, ES cells can be genetically tailored via homologous recombination (Smithies et al, 1985) (that is location and enzymatic recombination of an exogenous DNA fragment into the homologous endogenous sequence; Figure 1a and Supplementary Information) in vitro prior to blastocoel insertion, representing the superior technique.…”

Section: Transgenic Micementioning

confidence: 99%

Review: genetic models of acute myeloid leukaemia

2008

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The use of genetically engineered mice (GEM) have been critical in understanding disease states such as cancer, and none more so than acute myelogenous leukaemia (AML), a disease characterized by over 100 distinct chromosomal translocations. A substantial proportion of cases exhibiting recurrent reciprocal translocations at diagnosis, such as t(8;21) or t(15;17) have been exhaustively studied and are currently employed in clinical diagnosis. However, a definitive conclusion regarding the leukaemogenic potential of defined transgenes for this disease remains elusive. While it is increasingly apparent that a number of cooperating mutations are necessary to develop a leukaemic phenotype, the number of models reflecting these synergisms remains few. Furthermore, little emphasis has been paid to the effect of chromosomal translocations other than recurrent genetic abnormalities, with no models reflecting the multiple abnormalities observed in high-risk cases of AML accounting for 8-10% of adult AML. Here we review the differing technologies employed in generation of GEM of AML. We discuss the relevance of GEM AML from embryonic stem cell-mediated (for example retinoic acid receptor-a fusions and AML1/ETO) models; through to the valuable retroviral-mediated gene transfer models. The latter have been used to great effect in defining the transforming properties of chromosomal translocation products such as MLL (found in 5-6% of all AML cases) and NUP98 (denoting poor prognosis in therapy-related disease) and particularly when co-transduced with bad prognostic factors such as Flt3 mutations. Finally, we comment on the emergence of newer transduction technologies, which can regulate the level of expression to defined cell lineages in both primary murine and human xenografts, and discuss how combining multiple genetic modalities, more relevant models of this complex disease are being generated.

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Section: Transgenic Micementioning

confidence: 99%

Review: genetic models of acute myeloid leukaemia

2008

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“…109 Frequently, altered gene expression encoding transcriptional oncoproteins interfere with regulatory cascades critical for proliferation, differentiation and survival of normal blood precursors, which can subsequently be studied in transgenic animal models. While transgenic mice may be created 'classically' through direct pronuclear injection of exogenous DNA into fertilised zygotes [388][389][390] and succeeding implantation into a pseudopregnant female generating transgenic progeny, the method results in indiscriminate integration into the genome and is reliant upon overexpression of the transgene to generate a phenotype. Further alternatives include injection of genetically modified mouse embryonic stem (ES) cells into a blastocyst [391][392][393] (embryonic day 4.5) or embryonic retroviral infection.…”

Section: Transgenic Micementioning

confidence: 99%

Animal models of acute myelogenous leukaemia – development, application and future perspectives

2005

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From the early inception of the transplant models through to contemporary genetic and xenograft models, evolution of murine leukaemic model systems have been critical to our general comprehension and treatment of cancer, and, more specifically, disease states such as acute myelogenous leukaemia (AML). However, even with modern advances in therapeutics and molecular diagnostics, the majority of AML patients die from their disease. Thus, in the absence of definitive in vitro models which precisely recapitulate the in vivo setting of human AMLs and failure of significant numbers of new drugs late in clinical trials, it is essential that murine AML models are developed to exploit more specific, targeted therapeutics. While various model systems are described and discussed in the literature from initial transplant models such as BNML and spontaneous murine leukaemia virus models, to the more definitive genetic and clinically significant NOD/SCID xenograft models, there exists no single compendium which directly assesses, reviews or compares the relevance of these models. Thus, the function of this article is to provide clinicians and experimentalists a chronological, comprehensive appraisal of all AML model systems, critical discussion on the elucidation of their roles in our understanding of AML and consideration to their efficacy in the development of AML chemotherapeutics.

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“…The transgenic insert was prepared by cutting the plasmid with HindIII/PvuI and purified from the gel for microinjection. 75 l of the plasmid at 2 g/ml was injected into a fertilized egg of C57BL/6 mice and implanted into C57BL/6 recipient mice as described (28). Tails were clipped at weaning, and genomic DNA was extracted for genotyping.…”

Section: Methodsmentioning

confidence: 99%

The Role of p22 NF-E4 in Human Globin Gene Switching

Zhou

Zhao

Sutton

et al. 2004

Journal of Biological Chemistry

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The human stage selector protein, a complex containing the ubiquitous transcription factor CP2 and the erythroid-specific factor p22 NF-E4, facilitates the interaction of the ␥-globin genes with the locus control region in fetal erythroid cells. Enforced expression of p22 NF-E4 in K562 cells and human cord blood progenitors increases fetal globin gene expression, and in progenitors, reduces ␤-globin expression. To examine the role of NF-E4 in an in vivo model of hemoglobin switching, we enforced the expression of p22 NF-E4 in transgenic mice carrying the human ␤-globin locus yeast artificial chromosome. Although murine erythropoiesis and globin gene expression is unaffected in these mice, the expression profile of the human globin genes is altered. All three transgenic lines displayed an increased ␥:␤-globin ratio in E12.5-14.5 fetal liver, resulting in a delay in the fetal/adult switch. At E12.5, this is primarily due to a reduction of ␤-gene expression, whereas at E14.5, the increased ␥:␤ ratio is due to enhanced ␥-gene expression. Despite this, the switch in globin subtype is fully completed in the adult bone marrow. These findings indicate that p22 NF-E4 is capable of influencing human globin gene expression in vivo but is incapable of overriding the intrinsic mechanisms governing ␥-gene silencing in this context.

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[28] Gene transfer into mouse embryos: Production of transgenic mice by pronuclear injection

Cited by 206 publications

References 7 publications

Review: genetic models of acute myeloid leukaemia

Review: genetic models of acute myeloid leukaemia

Animal models of acute myelogenous leukaemia – development, application and future perspectives

The Role of p22 NF-E4 in Human Globin Gene Switching

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