Academic journal article Alcohol Research

Selected Lines and Inbred Strains

Academic journal article Alcohol Research

Selected Lines and Inbred Strains

Article excerpt

Tools in the Hunt for the Genes Involved in Alcoholism

In their quest to elucidate the genetic influences contributing to alcoholism, researchers have long used selected lines and inbred strains of rodents. Selected lines are obtained by repeatedly mating those animals within a population that show extremely high or low values of the desired trait. Inbred strains are generated by mating male and female siblings, irrespective of any particular trait, over several generations. Both of these approaches have provided researchers with extensive knowledge about the genetic and neurobiological mechanisms contributing to alcohol-related traits. However, the use of these models is associated with some limitations, mostly resulting from the inbreeding involved in generating such lines and strains. Nevertheless, these models can offer some advantages over other genetic approaches, such as the analysis of quantitative trait loci or the generation of transgenic and knockout mice. KEY WORDS: animal model; animal strains; animal selectively bred for AOD (alcohol or other drug) preference; selective breeding; genetic theory of AODU (AOD use, abuse, and dependence); phenotype; quantitative trait locus; gene knockout technology; transgenic technology

Breeding techniques to generate animals with desired traits have long been a staple of genetic research, inducing alcohol-related research. Two of the oldest techniques for studying the genetics of alcohol-related traits in animals are analyses of selected lines and of inbred strains, usually of rats or mice. The use of these animal models long predates the present revolution in molecular biology, because it does not necessitate advanced biological techniques. Like newer models using molecular genetic techniques, however, these breeding approaches are based on the concept of manipulating an animal's genetic material and studying the resulting effects on a behavior of interest.

Alcohol studies using selected lines and inbred strains rely on the study of groups, or populations, of animals that differ on a genetic level. At the same time, the animals' environment can be controlled rigorously in the laboratory setting. Under these conditions, comparisons of various populations allow alcohol researchers to investigate how genes can influence a wide variety of alcohol-related behaviors (e.g., alcohol consumption, tolerance, and withdrawal) as well as physiological traits that may be important in mediating alcohol's effects. This article briefly reviews the strategies used in generating selected lines and inbred strains. The article then discusses some of the applications of these models as well as some of the limitations associated with their use.

GENERATION OF SELECTED LINES

Selective breeding has long been used in agriculture to enhance desired characteristics (i.e., phenotypes) in both plants and animals. In the laboratory, researchers create selected lines by exploiting the natural variability inherent in an animal population and breeding those individuals that have either extremely high or extremely low values of the phenotype of interest. For example, in regard to alcohol withdrawal, researchers might mate either animals exhibiting the most severe withdrawal symptoms or animals exhibiting the mildest withdrawal symptoms. After several generations of selective breeding, the resulting lines will demonstrate stable differences in the phenotype of interest.

The most widely studied alcohol-related phenotype in selected lines has been free-choice alcohol drinking. Although many animals will not drink alcohol when given a choice between alcohol and water, great variability exists in the amount of alcohol individual animals within a population will consume. Selective breeding for differences in this phenotype was first initiated in the late 1940s, when Mardones and colleagues developed the UChA and UChB lines of rats that exhibit low and high levels of alcohol consumption, respectively (Mardones and Segovia-Riquelme 1983). …

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