High-level expressing YAC vector for transgenic animal bioreactors

The position effect is one major problem in the production of transgenic an imals as mammary gland bioreactors. In the present study, we introduced the human growth hormone (hGH) gene into 210-kb human alpha-lactalbumin positi on-independent YAC vectors using homologous recombination and produced tran sgenic rats via microinjection of YAC DNA into rat embryos. The efficiency of producing transgenic rats with the YAC vector DNA was the same as that u sing plasmid constructs. Ail analyzed transgenic rats had one copy of the t ransgene and produced milk containing a high level of AGH (0.25-8.9 mg/ml). In transgenic rats with the YAC vector in which the human cu-lactalbumin g ene was replaced with the hGH gene, tissue specificity of hGH mRNA was the same as that of the endogenous rat alpha-lactalbumin gene. Thus, the 210-kb human alpha-lactalbumin YAC is a useful vector far high-level expression o f foreign genes in the milk of transgenic animals. (C) 1999 Wiley-Liss, Inc .