One of the key elements to ensuring reproducibility in experimentation involving murine models of disease is to establish a consistent and defined genetic background on the model of study. Mutant alleles are often created in mixed genetic backgrounds, and experimental variability can be introduced when using wild type controls from an inbred strain, or with a genetic background that shifts at each new mating generation. The traditional back cross approach to create a congenic line is time consuming and costly. Utilizing a speed congenic approach can cut the time to create a congenic line nearly in half-saving cage costs and research time.
The primary goal of a speed congenic project is to greatly reduce the number of time-consuming breeder generations. GTCA customizes the approach to tailor fit to your line of interest. We combine knowledge of the inherent characteristics of the inbred lines involved, including breeding capabilities, known phenotypes and allele location to ensure the highest likelihood of success. It should be recognized, however that not every mutant allele is compatible with any particular genetic background. There are numerous instances where sub-viable or non-viable conditions arise that are genetic background dependent. Careful review of Mendelian ratios and expected phenotype development at each generation is imperative.
Starting at the N2 progeny generation, animals will first be screened for the mutant allele of interest. Genomic DNA from carriers of the allele will then be submitted for high density SNP scanning. The high-density SNP scanning can define the genetic background to include chromosomal sex determination, discrimination of substrains from multiple commercial vendors, and detection of constructs used in genetically engineered animals. The SNP scan results will be provided along with GTCA’s selection of animals to breed for the next generation.
At completion, a final report will be provided detailing methods and progression to the congenic line. This report can be archived with the line curation and can be used as a reference when publishing methods used to create the line.