knockout mouse(redirected from Knock-out mouse)
Experimental animals lacking specific genes have become valuable research tools in many branches of medicine, including genetics, physiology, pharmacology, immunology, cell biology, and oncology. A transgenic animal is one into whose genome a foreign gene, constructed by recombinant DNA technology, has been deliberately inserted. Placement of the inserted gene at a specific locus in the genome is made possible by incorporating it in a vector in which it is flanked by DNA sequences unique to the target site. The artificial genetic material is introduced into an embryo, which then develops into a chimera whose tissues contain both normal cells and cells containing the transgene. Matings among such animals yield some offspring that are homozygous for the transgene. If the inserted gene is a nonfunctional (null) allele, it deletes or "knocks out" the normal, wild allele. Not only is the deleted gene not expressed, but the offspring of matings among homozygous individuals constitute a pure strain, all of whose members lack the gene. Although theoretically any animal could be subjected to the knockout technique, mice have been used almost exclusively. Mice are small and easily maintained and they reproduce rapidly and have a short life span. In addition, mouse and human genomes are strikingly similar, with about 75% correspondence of genes. That knockout mice lacking a wide variety of genes are often phenotypically normal indicates that the mouse genome, like that of human beings, often has sufficient redundancy to compensate for a single missing pair of alleles. Knockout mice lacking the p53 tumor suppressor gene are used in studies of carcinogenesis, and those lacking the gene for the low-density lipoprotein (LDL) receptor constitute an animal model of human familial hypercholesterolemia. Knockout mice have proved valuable in revealing the functions of genes for which mutant strains were not previously available.