The ability to introduce functional genes into organisms provides a powerful tool for studying complex biological processes. Gene transfer is especially valuable in diploid organisms with long life cycles where classical genetic approaches are impractical. Over the past 15 years, various methods have been developed to introduce foreign DNA into both somatic and germ cells of mammals. The most prevalent technique for introducing genes into the germ line is direct microinjection of cloned DNA into pronuclei of fertilized eggs. This method has been used extensively to produce transgenic mice, which carry foreign genes in their genome. These genes can be expressed in somatic and germ cells, and offspring of transgenic founder mice often continue to express the foreign genes. The integration of foreign DNA into the genome is usually random, and the foreign DNA can be incorporated into various chromosomes. The mechanism of integration is not fully understood, but it is believed that chromosomal breaks play a role in the integration process. The foreign DNA is stably transmitted for many generations with no evidence of rearrangement. However, some examples have been reported in which transgenes were rearranged, partially deleted, or amplified. In addition to microinjection of pronuclei, foreign DNA has been incorporated into the genome of mice by microinjection into the cytoplasm, nuclei of two-cell embryos, and the blastocoel cavity. Infection of preimplantation embryos with retroviruses has also been successful. This technique is currently receiving considerable attention because it offers some useful advantages over microinjection for certain applications. Another method of introducing genes into the germ line involves introducing DNA into totipotent teratocarcinoma cells or embryonic stem cells and then incorporating these cells into the blastocyst of developing embryos. The expression of genes in transgenic mice is often tissue-specific, and some genes are expressed in a tissue-specific manner. The expression of genes in transgenic mice can be influenced by various factors, including the chromosomal location of the gene, the presence of enhancer elements, and the presence of silencer sequences. The expression of genes in transgenic mice can also be affected by environmental signals. Some genes are not expressed or are expressed with very low frequency. The expression of some genes can be influenced by prokaryotic vector sequences. The expression of some genes can also be affected by the presence of cis-acting "silencer" sequences. The expression of genes in transgenic mice can vary among different offspring, and this variability can be due to various factors, including methylation of the DNA. The expression of genes in transgenic mice can also be affected by the presence of enhancer elements. The expression of genes in transgenic mice can be influenced by the presence of various regulatory elements, including promoters, enhancers, silencers, matrix attachment sites, topoisomerase-binding sites, and origins of DNA replication. The expression of genes in transgenic mice can also be affected by the presence of various epistThe ability to introduce functional genes into organisms provides a powerful tool for studying complex biological processes. Gene transfer is especially valuable in diploid organisms with long life cycles where classical genetic approaches are impractical. Over the past 15 years, various methods have been developed to introduce foreign DNA into both somatic and germ cells of mammals. The most prevalent technique for introducing genes into the germ line is direct microinjection of cloned DNA into pronuclei of fertilized eggs. This method has been used extensively to produce transgenic mice, which carry foreign genes in their genome. These genes can be expressed in somatic and germ cells, and offspring of transgenic founder mice often continue to express the foreign genes. The integration of foreign DNA into the genome is usually random, and the foreign DNA can be incorporated into various chromosomes. The mechanism of integration is not fully understood, but it is believed that chromosomal breaks play a role in the integration process. The foreign DNA is stably transmitted for many generations with no evidence of rearrangement. However, some examples have been reported in which transgenes were rearranged, partially deleted, or amplified. In addition to microinjection of pronuclei, foreign DNA has been incorporated into the genome of mice by microinjection into the cytoplasm, nuclei of two-cell embryos, and the blastocoel cavity. Infection of preimplantation embryos with retroviruses has also been successful. This technique is currently receiving considerable attention because it offers some useful advantages over microinjection for certain applications. Another method of introducing genes into the germ line involves introducing DNA into totipotent teratocarcinoma cells or embryonic stem cells and then incorporating these cells into the blastocyst of developing embryos. The expression of genes in transgenic mice is often tissue-specific, and some genes are expressed in a tissue-specific manner. The expression of genes in transgenic mice can be influenced by various factors, including the chromosomal location of the gene, the presence of enhancer elements, and the presence of silencer sequences. The expression of genes in transgenic mice can also be affected by environmental signals. Some genes are not expressed or are expressed with very low frequency. The expression of some genes can be influenced by prokaryotic vector sequences. The expression of some genes can also be affected by the presence of cis-acting "silencer" sequences. The expression of genes in transgenic mice can vary among different offspring, and this variability can be due to various factors, including methylation of the DNA. The expression of genes in transgenic mice can also be affected by the presence of enhancer elements. The expression of genes in transgenic mice can be influenced by the presence of various regulatory elements, including promoters, enhancers, silencers, matrix attachment sites, topoisomerase-binding sites, and origins of DNA replication. The expression of genes in transgenic mice can also be affected by the presence of various epist