Unusual metabolic characteristics in skeletal muscles of transgenic rabbits for human lipoprotein lipase

BACKGROUND: The lipoprotein lipase (LPL) hydrolyses circulating triacylglycerol-rich lipoproteins. Thereby, LPL acts as a metabolic gate-keeper for fatty acids partitioning between adipose tissue for storage and skeletal muscle primarily for energy use. Transgenic mice that markedly over-express LPL exclusively in muscle, show increases not only in LPL activity, but also in oxidative enzyme activities and in number of mitochondria, together with an impaired glucose tolerance. However, the role of LPL in intracellular nutrient pathways remains uncertain. To examine differences in muscle nutrient uptake and fatty acid oxidative pattern, transgenic rabbits harboring a DNA fragment of the human LPL gene (hLPL) and their wild-type littermates were compared for two muscles of different metabolic type, and for perirenal fat. RESULTS: Analyses of skeletal muscles and adipose tissue showed the expression of the hLPL DNA fragment in tissues of the hLPL group only. Unexpectedly, the activity level of LPL in both tissues was similar in the two groups. Nevertheless, mitochondrial fatty acid oxidation rate, measured ex vivo using [1-(14)C]oleate as substrate, was lower in hLPL rabbits than in wild-type rabbits for the two muscles under study. Both insulin-sensitive glucose transporter GLUT4 and muscle fatty acid binding protein (H-FABP) contents were higher in hLPL rabbits than in wild-type littermates for the pure oxidative semimembranosus proprius muscle, but differences between groups did not reach significance when considering the fast-twitch glycolytic longissimus muscle. Variations in both glucose uptake potential, intra-cytoplasmic binding of fatty acids, and lipid oxidation rate observed in hLPL rabbits compared with their wild-type littermates, were not followed by any modifications in tissue lipid content, body fat, and plasma levels in energy-yielding metabolites. CONCLUSIONS: Expression of intracellular binding proteins for both fatty acids and glucose, and their following oxidation rates in skeletal muscles of hLPL rabbits were not fully consistent with the physiology rules. The modifications observed in muscle metabolic properties might not be directly associated with any LPL-linked pathways, but resulted likely of transgene random insertion into rabbit organism close to any regulatory genes. Our findings enlighten the risks for undesirable phenotypic modifications in micro-injected animals and difficulties of biotechnology in mammals larger than mice

Substitution of the α-lactalbumin transcription unit by a CAT cDNA within a BAC clone silenced the locus in transgenic mice without affecting the physically linked Cyclin T1 gene

We recently reported that a goat bacterial artificial chromosome (BAC) clone conferred site-independent expression in transgenic mice of the two loci present within its insert, the ubiquitously expressed Cyclin T1 and the mammary specific β-lactalbumin (αlac) genes. To assess if this vector could target mammary-restricted expression of cDNA, the CAT ORF was introduced by homologous recombination in Escherichia coli in place of the αlac transcription unit. The insert of this modified BAC was injected into mice and three transgenic lines were derived. None of these lines expressed the CAT gene suggesting that the use of long genomic inserts is not sufficient to support the expression of intron-less transgenes. The physically linked goat Cyclin T1 locus was found to be active in all three lines. This observation reinforced the hypothesis that the two loci are localised in two separate chromatin domains

Position-independent and tissue specific expression of a porcine whey acidic protein gene from bacterial artificial chromosome in transgenic mice

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Position-independent and tissue specific expression of a porcine whey acidic protein gene from bacterial artificial chromosome in transgenic mice

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Position-independent and tissue-specific expression of porcine whey acidic protein gene from a bacterial artificial chromosome in transgenic mice

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Cloned rabbits produced by nuclear transfer from adult somatic cells

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Préparer l’intervention des sapeurs-pompiers en laboratoire confiné

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La religión bajo la perspectiva evolucionista de Daniel Dennett

La intención que guía este trabajo es caracterizar la posición que Dennett, desde su perspectiva de la teoría evolutiva, asume frente a la religión. Bajo una metodología descriptiva este artículo da a conocer el escenario desde el cual Dennett estudia la religión en medio de grandes avances científicos y del resquebrajamiento de las formas institucionales, entendiendo que, si bien su crítica, por darse fuera de las líneas rectoras de una reflexión tradicional del fenómeno religioso, puede parecer infundada, ella va a incidir, se quiera o no, gracias a la gran divulgación del pensamiento de Dennett, en la percepción que van a tener no solo las personas de la calle, sino incluso los nuevos teóricos de la religión. La crítica de Dennett a la religión no agota sin embargo, una gran convicción: si bien la persona sale del mundo, de la materialidad y de la animalidad, se levanta y emerge por encima del mundo de la cultura y de la libertad en busca de su último sentido, que merece ser llamado Dios

Recombinant human extracellular superoxide dismutase produced in milk of transgenic rabbits

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Effect of the rabbit alphas1-casein gene distal enhancer on the expression of a reporter gene in vitro and in vivo

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