[en] Double-muscling in cattle is a generalised hypertrophy of skeletal muscle resulting from a hyperplasia of the myofibers. Using a positional cloning strategy, we have identified the gene underlying double-muscling, namely myostatin, and causal loss-of-function mutations therein. Myostatin is a novel member of the TGF-beta superfamily of growth and differentiation factors. Using conditional gene targeting in a murine model, we have demonstrated that post-natal muscle specific inactivation of the myostatin gene causes full-blown double muscling. This demonstrates the potential value of myostatin antagonist whether to promote muscle regeneration in patients suffering from muscle wasting disease, or to enhance meat production in livestock species. Finally, by targeting a myostatin transinhibitor on the Y chromosome, we have demonstrated in the mouse the feasibility of a more efficient cattle production system combining superior beef production abilities for bulls and dairy abilities for cows. [fr] Le caractère culard chez le bovin est une augmentation généralisée de la masse des muscles squelettiques faisant suite à une hyperplasie des fibres musculaires. En utilisant des méthodes classiques de clonage positionnel, nous avons démontré que le caractère culard du bovin est dû à des mutations induisant une perte de fonction de la myostatine, un membre de la superfamille des facteurs de croissance et de différenciation de type TGF-? . Les outils de ciblage et d’inactivation conditionnelle de gènes chez la souris nous ont ensuite permis de montrer que l’inactivation postnatale et muscle-spécifique de la myostatine suffisait à induire une hypertrophie musculaire comparable à celle observée lors de l’inactivation constitutive du même gène, ouvrant ainsi la porte à l’utilisation d’inhibiteurs de la myostatine chez l’adulte, tant dans le domaine des productions animales qu’en médecine humaine. Enfin, en insérant un transinhibiteur de la myostatine sur le chromosome Y, nous avons montré en modèle murin la faisabilité d’un nouveau mode d’élevage bovin où les caractères viandeux et laitiers ségrégeraient au sein d’une même race, respectivement chez les mâles et les femelles.
Disciplines :
Veterinary medicine & animal health
Author, co-author :
Pirottin, Dimitri ; Université de Liège - ULiège > Département de productions animales > Génomique animale
Grobet, L.
Georges, Michel ; Université de Liège - ULiège > Département de productions animales > Génomique animale
Language :
French
Title :
Positional cloning and genetic engineering of the myostatin gene causing double muscling in cattle
Alternative titles :
[fr] Clonage positionnel et ingénierie génétique de la myostatine, le gène responsable du caractère culard chez les bovins
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