Abstract: The present invention relates to methods of producing an allelic series of modifications in genes of interest in a cell. In particular, the invention provides methods for using nucleic acid sequence-modifying agents (e.g., chemicals, electromagnetic radiation, etc.) to introduce modifications in any nucleic acid sequence in the genome of a cell. Also provided are sets of cells which contain at least one modification in any gene of interest. The methods and compositions of the invention are useful in determining the function of the gene of interest.

Abstract: The present invention relates to methods of producing an allelic series of modifications in genes of interest in a cell. In particular, the invention provides methods for using nucleic acid sequence-modifying agents (e.g., chemicals, electromagnetic radiation, etc.) to introduce modifications in any nucleic acid sequence in the genome of a cell. Also provided are sets of cells which contain at least one modification in any gene of interest. The methods and compositions of the invention are useful in determining the function of the gene of interest.

Abstract: The present invention provides non-human transgenic animals in which an antibody subtype is selectively inactivated such that the transgenic animals express a reduced level of IgG3 relative to the levels expressed by the corresponding wild-type animal. Selective inactivation is achieved by the disruption through homologous recombination of the a nucleic acid sequence which encodes a constant region in the antibody subtype. The present invention provides transgenic animals which contain a disrupted C.gamma.3 gene. These transgenic animals retain the ability to express other antibody isotypes and subtypes. The present invention further provides methods for using these transgenic animals for screening candidate therapeutic compounds and for producing monoclonal antibodies which contain reduced levels of IgG3.