Abstract: Methods of generating modified embryos and mammals by introduction of donor cells into an early stage embryo are provided, such that the resulting embryo and animal generated therefrom has a significant or complete contribution to all tissues from the donor cells and is capable of transmitting the donor cell DNA.

Abstract: Methods for modifying a mammalian cell target such that the presence of a Y chromosome is detectable. The method includes construction of a targeting vector with a detectable marker that can recombine or insert into a pre-selected site on the Y chromosome, allowing the presence of the Y chromosome to be detectable through the presence of the integrated detectable marker. The method can be used to distinguish male from female embryos.

Abstract: A method for engineering and utilizing large DNA vectors to target, via homologous recombination, and modify, in any desirable fashion, endogenous genes and chromosomal loci in eukaryotic cells. These large DNA targeting vectors for eukaryotic cells, termed LTVECs, are derived from fragments of cloned genomic DNA larger than those typically used by other approaches intended to perform homologous targeting in eukaryotic cells. Also provided is a rapid and convenient method of detecting eukaryotic cells in which the LTVEC has correctly targeted and modified the desired endogenous genes(s) or chromosomal locus (loci) as well as the use of these cells to generate organisms bearing the genetic modification.

Abstract: Methods of improving gene targeting comprising using a ubiquitin promoter to drive drug resistance gene expression are provided. Such improvements include increasing ES cell colony survival and targeting frequency.

Abstract: Methods of creating mutations in genomic exons by inserting introns into the genomic exons via homologous recombination. Also, methods are provided for introducing modifications into genomic exons by inserting introns into the genomic exons via homologous recombination such that a mature mRNA transcript produced from a genomic region of the genome comprising the genomic exon does not contain the modification are provided. The methods provide for a rapid method for introducing mutations and/or modifications of any type into a mammalian cell genome.