Gene targeting technology for creating transgenic models of lymphopoiesis

Naturally occurring immunodeficient mouse strains express a variety of genetic defects in myeloid and/or lymphoid cell development. These strains have served as valuable animal models for studying immune cell differentiation and mechanisms of transplant rejection. Some of the most commonly used strains carry mutations at the nude, scid, beige, and/or xid loci. Gene targeting technology can now be used to directly modify endogenous alleles via homologous recombination with exogenous DNA. By performing DNA targeting in embryonic stem (ES) cells, germline transmission of these modifications can be obtained by breeding chimeras generated from cloned ES cells. This approach can be used to target the inactivation, modification, or replacement of specific genes and has been used to examine the role of several alleles in hematopoiesis. This review describes the use of this technology to generate mutations that influence the development and function of T and B lymphocytes.