Deletion of repetitive gene families

With the complete sequencing of the human and mouse genomes a large number of genes have been discovered. Many of these genes are found grouped together on chromosomes and are highly related. Current technology for studying individual genes in mice is not adequate to study the role of highly repetitive and related gene families. The engineering of chromosomes in mouse embryonic stem cells offers a way to delete these large gene families and to then produce a gene family-deficient mouse, which can be used to study the possible role of these genes in humans. The natural killer gene complex on mouse chromosome 6 is a perfect genetic playground to perfect chromosome deletion in mouse ES cells. The NKC is the home of several different gene families (Ly49, Nkrp1, Nkg2) that govern the function of natural killer cells, a type of white blood cell that fights viral infections and cancers. We plan to optimize the available deletion technology using these NKC gene families. Success here will benefit several fields of research including immunology (NKC, IFN), developmental biology (Hox), and neuroscience (olfaction), each of which has repetitive gene family models that require scrutiny, but lack proper technological tools.