The Use of Yeast Artificial Chromosomes for Transgenesis

Abstract

This chapter integrates and expresses foreign genes in the mouse germline has brought about considerable advances in biomedical research. The option of co-lipofecting a drug-selectable marker on a separate plasmid was chosen by Choi et al. with a 100 kb Yeast Artificial Chromosomes (YAC) covering an 85 kb human heavy chain immunoglobulin genomic fragment. This resulted in a very low efficiency of transfection, most of the resistant ES cell clones carrying fragmented YAC pieces. Similarly, a YAC carrying the human PAX-6 gene was shown to rescue the small eye phenotype in transgenic mice. Surprisingly, overexpression of the PAX-6 gene in mice with a high copy number of the transgene resulted in severe abnormalities in the development of the eye, emphasising the importance of the strict regulation of this gene during development. Atherosclerosis is another human disease where creation of YAC transgenic mice has contributed significantly towards establishing an animal model.