Applications of animal transgenesis

Transgenesis is the introduction of a new gene in a whole organism to generate animal lines harbouring new genetic traits or having lost a gene. This procedure helps our understanding of the mechanisms regulating gene expression as well as the function of genes in the body. Transgenesis provides models to study human diseases and prepares animals as potential sources of organs and cells, as well as pharmaceutical proteins, to be used in man. Transgenesis creates genetically modified farm animals, thereby increasing and targeting biodiversity. However, the success of animal transgenesis is still restricted by several problems, particularly technical and financial. Gene transfer remains difficult in large animals even if new techniques have brought decisive improvements. Another problem is the often poorly controlled expression of transgenes. This requires the generation of multiple founders to keep only the best, and reduce the unpredictable side effects of transgenesis. The applications of transgenesis in farm animals are also limited by the availability of genes expected to bring a significant improvement over pre-existing lines. Animal transgenesis must also deal with issues of biosafety and acceptability by consumers. This article reviews the major advances in animal transgenesis.La transgenèse offre la possibilité de replacer un gène dans son environnement complexe qu'est un organisme entier et de créer des lignées d'animaux portant des caractères génétiques nouveaux ou ayant perdu un gène. Ceci permet de mieux comprendre les mécanismes de la régulation de l'expression des gènes mais aussi leur fonction dans l'organisme. La transgenèse permet de créer des modèles pour l'étude de maladies humaines et de préparer des animaux qui sont potentiellement des sources d'organes et de cellules pour l'homme mais aussi de protéines thérapeutiques. Les animaux d'élevage peuvent être génétiquement modifiés et bénéficier ainsi d'un accroissement accéléré et ciblé de la diversité génétique. Les succès de la transgenèse animale se heurtent encore à divers problèmes notamment techniques et financiers. Le transfert de gène reste difficile chez les gros animaux même si de nouvelles techniques ont apporté des progrès décisifs. Un autre problème est celui de l'expression des transgènes qui est souvent mal contrôlée. Ceci oblige à multiplier le nombre des animaux fondateurs de lignées pour ne garder que les meilleurs et pour limiter les effets secondaires imprévisibles de la transgenèse. Les applications de la transgenèse aux animaux d'élevages sont également limitées par la disponibilité de gènes susceptibles d'apporter une amélioration significative des lignées préexistantes. Les applications de la transgenèse animale doivent également faire face à des problèmes de biosécurité et d'acceptabilité par les consommateurs. Cette revue se propose de faire le point sur les avancées de la transgenèse animale

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

Genetically modified animals from life-science, socio-economic and ethical perspectives: examining issues in an EU policy context

The interdisciplinary EC consortium (the PEGASUS project) aimed to examine the issues raised by the development, implementation and commercialisation of genetically modified (GM) animals, and derivative foods and pharmaceutical products. The results integrated existing social (including existing public perception) environmental and economic knowledge regarding GM animals to formulate policy recommendations relevant to new developments and applications. The use of GM in farmed animals (aquatic, terrestrial and pharmaceutical) was mapped and reviewed. A foresight exercise was conducted to identity future developments. Three case studies (aquatic, terrestrial and pharmaceutical) were applied to identify the issues raised, including the potential risks and benefits of GM animals from the perspectives of the production chain (economics and agri-food sector) and the life sciences (human and animal health, environmental impact, animal welfare and sustainable production). Ethical and policy concerns were examined through application of combined ethical matrix method and policy workshops. The case studies were also used to demonstrate the utility of public engagement in the policy process. The results suggest that public perceptions, ethical issues, the competitiveness of EU animal production and risk-benefit assessments that consider human and animal health, environmental impact and sustainable production need to be considered in EU policy development. Few issues were raised with application in the pharmaceutical sector, assuming ethical and economic issues were addressed in policy, but the introduction of agricultural GM animal applications should be considered on a case-by-case basis

Regulations endocrine, autocrine et paracrine du developpement de la glande mammaire

National audienc

Recent data on the mechanism of action of prolactin

106 ref.International audienc

La transgenèse animale et ses applications

National audienceTransgenic animals were obtained for the first time 17 years ago, This technique is widely used in basic research, Genes can be added, inactivated or specifically replaced in the genome of animals. This technical approach brings invaluable and numerous informations on the genome working and on the control mechanisms of biological functions. The production of recombinant proteins in the milk of transgenic animals is about to become an industrial activity, The transfer of organs (heart, kidney lung...) and cells (pancreas, liver...) from transgenic pigs to humans seems no more inaccessible, The use of transgenesis to improve animal production is still almost inexistent, It is restricted essentially to the obtention of models to study particular genes and biological functions. The technical difficulty and the cost to generate transgenic farm animals remain one of the major limitations for the applications in this field, However, gene transfer into cultured foetal cells followed by their transfer into enucleated oocytes to generate living animals should greatly contribute to improve this situation, Transgenic farm animals having interesting genetic traits should be obtained in the coming years. However, transgenesis will not be used instead of other methods (selection, vaccination. control of reproduction..,) which are also making quite significant progress. Transgenesis is rather an additional technique to improve animal production.La transgenèse animale a été réalisée avec succès pour la première fois il y a 17 ans. De nombreuses utilisations de cette technique existent pour la recherche fondamentale. Elles consistent à ajouter, à inactiver ou à remplacer spécifiquement des gènes dans les génomes des animaux. Ces expériences apportent une moisson d’informations incomparables sur le fonctionnement du génome et sur les mécanismes de régulation des fonctions biologiques. De nombreux modèles animaux sont également obtenus pour l’étude de maladies humaines. La production de protéines recombinantes dans le lait d’animaux transgéniques est en passe de devenir une réalité industrielle. Le transfert de certains organes (coeur, rein, poumon...) et cellules (pancréas, foie) de porcs transgéniques à l’espèce humaine est un objectif qui ne paraît plus inaccessible. Les applications de la transgenèse pour l’amélioration des productions animales sont encore à peu près inexistantes. Elles se cantonnent essentiellement à l’obtention de modèles pour des études de gènes et de fonctions biologiques particulières. La difficulté et le coût de la transgenèse chez les animaux domestiques sont une des causes essentielles de la lenteur des applications dans ce domaine. Toutefois, le transfert de gène dans des cellules foetales cultivées suivi de leur transfert dans des ovocytes énucléés devrait contribuer grandement à améliorer cette situation. La transgenèse appliquée directement aux animaux d’élevage pour obtenir de nouvelles lignées ayant des caractéristiques génétiques intéressantes a toutes les chances de s’imposer dans les années qui viennent. La transgenèse ne saurait toutefois se substituer aux autres techniques (sélection génétique, vaccination, maîtrise de la reproduction...) qui elles-mêmes font de rapides progrès pour améliorer la production animale. La transgenèse doit plutôt être considérée comme une technique supplémentaire pour améliorer les productions animales

La transgenese animale

National audienc

The biosafety problems of transgenic animals

chap. 81International audienc

Clonage, transgenèse et thérapie cellulaire

National audienc