Engineering of the murine myostatin gene in es cells in order to generate cre-loxp-based conditional and inducible mstn on to off and mstn off to on mice strains

Naturally occurring Myostatin knock-out cattle exhibit a hypermuscled phenotype (Grobet et al., Nature Genetics 1997,17, 71-74; Mammalian Genome 1998,9,210-213). Moreover, experimental knockout mice are also characterized by a spectacular muscle hypertrophy (McPherron et al., Nature 1997, 387, 83-90). To unravel some aspects of myostatin biology the murine gene has been engineered for gene targeting. Two strategies based on the Cre-LoxP site specific recombination system have been designed which are essentially aimed at (I) producing conditional knock-out mice lines driven by different patterns of Cre expression, (II) generating mice strains where a non-functional myostatin allele could be reversed to functionality conditional to Cre expression. Homologous recombinant ES cell lines with the desired features have been obtained for both constructs. Transient expression of Cre in the positive clones is underway to delete the floxed selection markers and to test for the functionality of the systems. Our final aim is to address fundamental aspects of myostatin biology as well as to experiment with the feasibility of new strategies in animal production on a murine model (e.g., to induce hypermuscularity of genetic origin after birth which could reduce the need for cesarean section in some cattle breeds).