Introduction and expression of the bacterial glyoxylate cycle genes in transgenic mice

Saini, Kulvinder Singh; Byrne, Carolyn; Leish, Z.; Pruss, Cathy A.; Rigby, N.W.; Brownlee, A.; Nancarrow, C. D.; Ward, Kevin

doi:10.1007/bf01980212

Cited by 8 publications

(3 citation statements)

References 24 publications

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“…The glyoxylate cycle is well characterized in microorganisms, higher plants [ 26 ] and nematods, but the occurrence and functionality in vertebrates, such as rodents, chickens or humans [ 7 - 11 ], is still a matter of debate. This has been attributed to the lack of this metabolic pathway, reduced expression of ICL/MS in normal conditions, or improper induction or measurement of the activity of these enzymes [ 27 ].…”

Section: Resultsmentioning

confidence: 99%

“…Despite the apparent success of this gene transfer, some aspects and limitations should be taken into account, such as the administered dose, which may affect liver function, as described by others [ 17 , 18 ], the limited number of animals in this translational research or the short period of time analyzed given that fasting can not be maintained at long term [ 27 ], among others.…”

Section: Resultsmentioning

confidence: 99%

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Fat-to-glucose interconversion by hydrodynamic transfer of two glyoxylate cycle enzyme genes

et al. 2008

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The glyoxylate cycle, which is well characterized in higher plants and some microorganisms but not in vertebrates, is able to bypass the citric acid cycle to achieve fat-to-carbohydrate interconversion. In this context, the hydrodynamic transfer of two glyoxylate cycle enzymes, such as isocytrate lyase (ICL) and malate synthase (MS), could accomplish the shift of using fat for the synthesis of glucose. Therefore, 20 mice weighing 23.37 ± 0.96 g were hydrodinamically gene transferred by administering into the tail vein a bolus with ICL and MS. After 36 hours, body weight, plasma glucose, respiratory quotient and energy expenditure were measured. The respiratory quotient was increased by gene transfer, which suggests that a higher carbohydrate/lipid ratio is oxidized in such animals. This application could help, if adequate protocols are designed, to induce fat utilization for glucose synthesis, which might be eventually useful to reduce body fat depots in situations of obesity and diabetes.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Fat-to-glucose interconversion by hydrodynamic transfer of two glyoxylate cycle enzyme genes

et al. 2008

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“…This DNA has been introduced into mammalian cells in culture and shown to be actively transcribed and translated into the appropriate enzymes (Byrne, 1990;, a valuable piece of information that demonstrates that the glyoxylate cycle can apparently co-exist with existing biochemistry in a mammalian cell without sequestering the new enzymes in speci®c organelles. The same gene has also been inserted into transgenic mice and has been shown to be expressed in a variety of tissues including the liver and small intestine (Saini et al 1996). The level of expression in these animals was not as high as that found for the gene MTCEK1 and the reason for this is not yet known.…”

Section: The Modi®cation Of Intermediary Metabolismmentioning

confidence: 99%

Altering nutrient utilization in animals through transgenesis

Ward

1999

Nutr. Res. Rev.

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Improved domestic animal productivity is necessary in order to provide for an increasing world population over the next two to three decades and such improvement would be aided by an increase in the ef®ciency of nutrient utilization. This can be achieved by conventional genetic selection protocols but progress by this approach is slow. A more rapid but as yet largely unproven technique is the direct modi®cation of the genome which can be achieved by the transfer of recombinant DNA to the nuclei of early embryos. This new technology is potentially powerful because it allows the direct transfer of genes without regard to inter-species barriers to breeding. However, it raises a new set of problems associated with the integration and expression of the foreign genetic information in the new genome. In this review the application of the technology to increasing nutrient utilization and increased productivity are discussed. Two areas have received substantial attention in the 15 years since the technique was ®rst applied to domestic animals. First, the current status of the modi®cation of growth hormone levels to improve productivity and feed utilization ef®ciency is reviewed, with current results suggesting that several of the projects may soon be approaching ®eld trial status.

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Expression of threonine-biosynthetic genes in mammalian cells and transgenic mice

Zhang

Dai

et al. 2014

Amino Acids

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Threonine is a nutritionally essential amino acid (EAA) for the growth and development of humans and other nonruminant animals and must be provided in diets to sustain life. The aim of this study was to synthesize threonine in mammalian cells through transgenic techniques. To achieve this goal, we combined the genes involved in bacterial threonine biosynthesis pathways into a single open reading frame separated by self-cleaving peptides (2A) and then linked it into a transposon system (piggyBac). The plasmids pEF1a-IRES-GFP-E2F-his and pEF1a-IRES-GFP-M2F-his expressed Escherichia coli homoserine kinase and threonine synthase efficiently in mouse cells and enabled cells to synthesize threonine from homoserine. This biosynthetic pathway occurred with a low level of efficiency in transgenic mice. Three transgenic mice were identified by Southern blot from 72 newborn mice, raising the possibility that a high level of expression of these genes in mouse embryos might be lethal. The results indicated that it is feasible to synthesize threonine in animal cells using genetic engineering technology. Further work is required to improve the efficiency of this method for introducing genes into mammals. We propose that the transgenic technology provides a promising means to enhance the synthesis of nutritionally EAAs in farm animals and to eliminate or reduce supplementation of these nutrients in diets for livestock, poultry and fish.

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Introduction and expression of the bacterial glyoxylate cycle genes in transgenic mice

Cited by 8 publications

References 24 publications

Fat-to-glucose interconversion by hydrodynamic transfer of two glyoxylate cycle enzyme genes

Fat-to-glucose interconversion by hydrodynamic transfer of two glyoxylate cycle enzyme genes

Altering nutrient utilization in animals through transgenesis

Expression of threonine-biosynthetic genes in mammalian cells and transgenic mice

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