YAC TRANSGENESIS IN FARM-ANIMALS - RESCUE OF ALBINISM IN RABBITS

The generation of transgenic mice with mammalian genes cloned in yeast artificial chromosomes (YACs) has generated great interest in the fie ld of gene transfer into livestock. Many of the problems associated wi th standard transgenesis-such as lack of crucial regulator elements an d position effects related to the integration site, which lead to vari ation in expression levels irrespective of the dose of the transgene-h ave been practically overcome. The large size of YAC-derived gene cons tructs (in excess of 1 Mb) facilitates the presence and transfer of al l elements required for the faithful regulation of a gene. With the ex periments discussed in this report, we have addressed the possibility of applying the obvious advantages of YAC transgenesis to farm animals . We have generated transgenic rabbits carrying a 250 kb YAC covering the mouse tyrosinase gene by pronuclear microinjection, and thus rescu ed the albino phenotype of the transgenic individuals. To date, this i s the first demonstration of a successful transfer of large genetic un its into the germ line of farm animals. This development might improve the occurrence of transgene expression at physiological levels and sp ecific sites in livestock. YAC transgenesis therefore will be applied in genetic engineering, for example, in the production of pharmacologi cally interesting proteins encoded by large gene units and generating transgenic donors for xenotransplantation. (C) 1996 Wiley-Liss, Inc.