In vivo modulation of human beta-globin gene switching

Abstract

Continuing accumulation of information from the genome projects requires parallel development of technologies to assess the in vivo functions of conserved sequences. We can now manipulate huge DNA molecules (such as yeast artificial chromosomes; YACs) in vivo, permitting the analysis of very large single genes or multigene loci as they exist in the chromosome. However, since transgenes integrate randomly into different chromatin environments, accurate evaluation of gene function in such transgenic mice is still fraught with pitfalls. We recently developed the use of cre-mediated homologous recombination to manipulate YAC transgenic mice in vivo, and successfully applied this strategy to the analysis of human beta-globin locus regulation. Here we describe these results and discuss the application of this technology to the analysis of this and related problems.