Non-additive inheritance of glucose phosphate isomerase activity in mice heterozygous at the<i>Gpi</i>-1<i>s</i>structural locus

West, John D.; Flockhart, Jean H.

doi:10.1017/s0016672300028342

Cited by 4 publications

(2 citation statements)

References 17 publications

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“…Upon injection into tetraploid B6D2F 2 blastocysts, ES cell lines of this genotype generated ES pups at an efficiency of 10 to 15%, comparable to the results obtained with other hybrid ES lines (4). The ES cell origin of these mice was confirmed by the analysis of glucose phosphate isomerase (GPI) isoenzymes (15) (18,29). The GPI a isoform was not detected in lysates from ES mice (Fig.…”

Section: Generation Of Wild-type Es Micesupporting

confidence: 74%

Hybrid Embryonic Stem Cell-Derived Tetraploid Mice Show Apparently Normal Morphological, Physiological, and Neurological Characteristics

Schwenk

Zevnik

Röhl

et al. 2003

Molecular and Cellular Biology

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ES cell-tetraploid (ES) mice are completely derived from embryonic stem cells and can be obtained at high efficiency upon injection of hybrid ES cells into tetraploid blastocysts. This method allows the immediate generation of targeted mouse mutants from genetically modified ES cell clones, in contrast to the standard protocol, which involves the production of chimeras and several breeding steps. To provide a baseline for the analysis of ES mouse mutants, we performed a phenotypic characterization of wild-type B6129S6F 1 ES mice in relation to controls of the same age, sex, and genotype raised from normal matings. The comparison of 90 morphological, physiological, and behavioral parameters revealed elevated body weight and hematocrit as the only major difference of ES mice, which exhibited an otherwise normal phenotype. We further demonstrate that ES mouse mutants can be produced from mutant hybrid ES cells and analyzed within a period of only 4 months. Thus, ES mouse technology is a valid research tool for rapidly elucidating gene function in vivo.The standard protocol to derive mouse mutants currently requires the production of germ line chimeras from heterozygous targeted embryonic stem (ES) cells, followed by at least two breeding steps to obtain homozygous mutants (2). Thus, the production of a mutant strain is a time-intensive task exceeding 12 months prior to the analysis of adult mutants. In addition, substantial resources are required for the breeding and genotyping of several hundred mice involved in a typical knockout project. Besides this classical approach, conditional gene targeting through Cre/LoxP-mediated recombination is increasingly used as it allows the spatial and temporal control of gene inactivation (13,21). Given that a Cre transgene needs to be introduced via additional breeding steps, the production of conditional knockout mice involves four reproductive cycles requiring at least 16 months before the target gene's function can be analyzed in vivo.Due to these extensive timelines, the impact of targeted mutants in high-throughput functional genome analysis is currently limited, creating a demand for a time-saving single-step procedure. Cloning of mice does not provide a viable alternative because the nuclear transplantation procedure is inefficient and a variety of abnormalities have been described in cloned mice which likely result from incomplete genome reprogramming (8,17,25,30). Alternatively, ES cell-tetraploid (ES) mice can be produced in a single step through the introduction of diploid ES cells into tetraploid blastocysts (16). The latter provide an initial host environment for the differentiation of ES cells but do not contribute to the embryo at later developmental stages. Although the methodology to produce ES mice from inbred ES cell lines was described more than a decade ago, its application was limited due to the extremely low frequency at which viable ES pups are recovered (16).Recently, this technology was significantly improved through the discovery that ES cell lines de...

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Section: Generation Of Wild-type Es Micesupporting

confidence: 74%

Hybrid Embryonic Stem Cell-Derived Tetraploid Mice Show Apparently Normal Morphological, Physiological, and Neurological Characteristics

Schwenk

Zevnik

Röhl

et al. 2003

Molecular and Cellular Biology

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“…After thawing, 50 /A of blood was added to 500 /A lysis buffer (01 M-triethanolamine, 1 mM-EDTA, pH 7-5 containing 5 mM-dithiothreitol and 0-5 mg/ml saponin), and the mixture was allowed to stand for ten min at 4 °C. A diminution in glucose phosphate isomerase activity between one and three months has also been reported (West et al 1987;West & Flockhart, 1989). in a Beckman microfuge 12, 250 fi\ of supernatant was diluted with 250 fil sample buffer (lysis buffer without saponin), G6PD was assayed and haemoglobin concentration measured using ar automatic enzyme analyser (ACP 5040, Eppendorf, Hamburg FRG) as described by Charles & Pretsch (1987).…”

Section: (I) Micementioning

confidence: 82%

Parental influences on expression of glucose-6-phosphate dehydrogenase,G6pd, in the mouse; a case of imprinting

Peters

Ball

1990

Genet. Res.

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Glucose-6-phosphate dehydrogenase (G6PD) activity was measured in blood from heterozygotes for the normal allele G6pda and the low activity allele G6pda-mlNeu. In adult mice lower activity was found in G6pda/G6pda-mlNeu than in the reciprocal heterozygote G6pda-mlNeu/G6pda (the maternal allele being listed first). Thus, either the paternally derived allele was over-expressed or the maternally derived allele was under-expressed. By contrast, in younger mice the difference in G6PD activity in reciprocal crosses was less marked. The findings are interpreted in terms of differential imprinting of maternally and paternally inherited information. The explanation offered for age related differences is that, as a consequence of imprinting, either the paternal X-chromosome is preferentially reactivated, or cells in which the paternally derived allele is active are at a selective advantage, and proliferate better than those in which the maternally inherited allele is active.

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Genetic differences in glucose phosphate isomerase activity among mouse embryos

West

Flockhart

1989

Development

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We have compared mouse embryos of three heterozygous, congenic genotypes (with high, medium and low levels of oocyte-coded glucose phosphate isomerase (GPI-1) activity respectively) to test whether 1) the survival time of oocyte-coded GPI-1 activity in the early embryo is affected by its activity level in the oocyte and 2) whether embryo-coded GPI-1 is detected earlier in embryos that inherit low levels of oocyte-coded GPI-1. The oocyte-coded GPI-1 was entirely GPI-1A allozyme in the high and medium groups but was the less stable GPI-1C allozyme in the low group. We determined total GPI-1 activity and the ratio of different GPI-1 allozymes in early embryos and calculated the activity of oocyte-coded and embryo-coded GPI-1. In all three groups, the oocyte-coded enzyme activity remained at a more or less constant level for the first 21 1/2 days. Some oocyte-coded GPI-1 remained in 4 1/2 day embryos from the high and medium groups but was gone by 5 1/2 days. Very little remained in 4 1/2 day embryos that inherited low levels of a less stable form of the enzyme (GPI-1C allozyme). Despite a 4- to 5-fold difference in initial oocyte-coded GPI-1 activity, no differences were seen among the three genotypically distinct groups of embryos in the time of activation of the embryonic Gpi-1s genes. The embryo-coded GPI-1 was first detectable in 3 1/2 day compacted morulae in all three groups. The level of oocyte-coded GPI-1, in the high group, when embryo-coded GPI-1 was first detected was higher than the level in the low group at any stage prior to detection of embryo-coded GPI-1.(ABSTRACT TRUNCATED AT 250 WORDS)

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Non-additive inheritance of glucose phosphate isomerase activity in mice heterozygous at theGpi-1sstructural locus

Cited by 4 publications

References 17 publications

Hybrid Embryonic Stem Cell-Derived Tetraploid Mice Show Apparently Normal Morphological, Physiological, and Neurological Characteristics

Hybrid Embryonic Stem Cell-Derived Tetraploid Mice Show Apparently Normal Morphological, Physiological, and Neurological Characteristics

Parental influences on expression of glucose-6-phosphate dehydrogenase,G6pd, in the mouse; a case of imprinting

Genetic differences in glucose phosphate isomerase activity among mouse embryos

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