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      Mouse is an extremely powerful tool in comparative genetic studies for its anatomical, physiological, and genetic similarities to humans preserved over the course of evolution. Similarities further manifest on the level of conserved linkage groups known as regions of synteny. For its extensive synteny to human chromosome 17 and for its unprecedented gene-density, we have chosen mouse chromosome 11 as our primary target for physical and functional analyses.

      Although generation of knockout mice has been proven to be an extraordinarily powerful tool in unraveling genetic and physiological properties of genes, its applicability is usually limited to a single locus. Using Cre-loxP recombination system in ES cells, we generated series of larger lesions. Some of them, primarily those in the region between Hsd17b1 (60.25cM) and Hoxb9 (56cM), are already established in the germ-line of mice. Mice carrying deficiencies that span throughout entire syntenic portion of chromosome 11 should emanate from this program to serve as a valuable resource in performing future haploid mouse genetics.

      Balancer chromosomes in combination with ENU mutagenesis constitute a powerful approach to uncover novel dominant and recessive phenotypes with a causative gene(s) likely to be found within the inversion interval. Using embryonic stem cell technology, balancer inversions are being generated. These inversions span the combined distance of 62 cM and are marked by recessive lethal mutations and coat color markers. Three generation crossing experiments between ENU mutagenized males and p53-Wnt3 inversion (24cM) carrying females have been just initiated and for detailed description of phenotypes generated please go to ENU mutagenesis.