Introduction: Genetically defined inbred, F1 hybrid, and genetically manipulated (transgenic, knock-out) rodents are important in research so that genomic variability can be controlled. Inbred strains can become contaminated and/or deviate to substrains with resultant significant and detectable changes in the genome (ILAR News 1982; 25(4):6-9; Science 1982; 217:379-381; Science 1983; 221:345; Science 1983; 221:625- 628; Science 1983; 221:1163; J Hered 1984; 75(3):171-174; Laboratory Animals 1984; 18(3):291-297; Lab Anim Sci 1991; 41(5): 471-3). These genetic alterations can have an insidious effect upon and even invalidate research depending on the degree of genome alteration and on the nature of the research. Additional benefits that can be derived from genetic monitoring include faster production of research models and reduced costs of colony maintenance.
Definition: Genetic monitoring is basically the assessment of the purity (or impurity) of a genome by observation and analysis of phenotypic expressions (i.e. coat color, protein synthesis, cell surface antigens, skeletal morphology, etc.) or by surveillance for specific nucleotide sequences. Any character determined by one gene or by multiple genes that can be measured and remain uninfluenced by environmental changes can be used to monitor a genotype.
Monitoring Outbred Stocks: The purpose of outbred stocks is to provide maximal genetic diversity (minimal inbreeding). Theoretically, the relative proportion of gene frequencies of all genes in outbred stocks should not change. In outbreds, spontaneous mutations and recombinations between mutant alleles supplement each other in generating and maintaining a multiple allelic system. Monitoring is geared towards the frequency of alleles in the colony, not their presence or absence. The goal of monitoring outbred stocks is to preserve heterogeneity and prevent subline formation. The methods utilized are biochemical markers and osteometric traits.
Monitoring Inbred Strains: The goals of monitoring are to (1) assure the genetic integrity of the given strain and (2) detect and eliminate of mutations. This is customarily done by establishing a genetic profile (i.e., coat color, alloantigens, constitutively expressed enzymes, molecular markers) and then comparing representative animals of the genotype to the profile. Commercial producers of inbred rodents habitually monitor their foundation and production colonies and make this information available for strains they sell.
Monitoring Genetically Manipulated Rodents: The purpose of monitoring is to both confirm the presence or absence of specific gene(s) and ensure the validity of the genetic background. The genetic background, be it inbred or outbred, may influence the expression of genes (Science 1995, 269: 230-4; Science 1995, 269: 234-8; Lab Animals 1996, 30: 127-31).
Techniques: A number of techniques are used and have been used historically for genetic monitoring. Most modern genetic monitoring programs are based upon molecular biology techniques. While the DAR does not offer genetic monitoring in-house, a number of commercial vendors offer these services and can be contacted for information.