New genetic technologies in alcohol research

Abstract

Recently developed approaches to creating genetically engineered animals have expanded researchers' repertoire of methods to investigate the roles of individual genes in the development of certain behaviors and diseases, including alcoholism. For example, knockout mice, in which single mouse genes have been inactivated, have allowed scientists to assess the roles of those genes in mediating some of alcohol's effects. This approach has been further refined using conditional gene knockout technology, which allows the inactivation of a gene only in certain cells or during specific developmental periods. Alternatively, transgenic mice (i.e., mice that carry a foreign gene in addition to their own genes) have been created in which researchers can activate or inactivate the foreign gene at will. Although these genetic engineering technologies have not yet been used extensively in alcohol research, they offer great promise in analyzing the functions of genes that may be involved in determining alcohol's effects on the body and the development of alcoholism.

Figure 1

Strategy for generating conventional knockout mice.

Figure 2

Strategy for generating conditional knockout mice. SOURCE: Adapted from Galli-Taliadoros et al. 1995.

Figure 3

Strategy for generating transgenic mice.

Figure 4

Schematic representation of an antibiotic-sensitive system to regulate the activity of a foreign gene (i.e., gene X) in transgenic mice. The activity of gene X in these animals is governed either by a protein called tetracycline-controlled transactivator (tTA) (A) or by a protein called reverse tetracycline-controlled transactivator (rtTA) (B). The genes encoding tTA or rtTA are introduced into the animals together with gene X. By adding an antibiotic to (or removing it from) the animals’ drinking water, one can control whether tTA and rtTA interact with the promoter that regulates the activity of gene X. Binding of tTA or rtTA to the promoter activates gene X, resulting in the production of the protein encoded by gene X. SOURCE: Adapted from Kistner et al. 1996.