Genetic monitoring is key to quality control of the breeding and production of inbred and transgenic lines of laboratory mice and rats. Taconic has established numerous production procedures that minimize the risk of genetic contamination. Our Genetic Monitoring Program is grounded in the identification of points in the production program where there is a higher risk of an undetected accidental mating or strain misidentification. By focusing genetic screening methods on these critical high-risk points, while scrutinizing quality control throughout, a genetic monitoring program can prevent a single mistake from becoming catastrophic.
Taconic's overall Genetic Monitoring Program is based on a combination of three strategies:
Visual characteristics of strains (most notably, coat color)
Production procedures that minimize co-localization and/or movement of strains of similar colors and that promote careful record keeping and strain segregation
Standard operating procedures outlining DNA-based marker and/or protein testing of animals at specific, defined, potentially risky points in the production process.
Cryopreservation of Taconic strains:
To avoid Genetic Drift, Taconic has embryos cryopreserved from strains and stocks that it provides.
Taconic refreshes all inbred stocks every 5 years or 10 generations whichever comes first.
Taconic Production Harmonization
Inbred Production: Taconic has only one Foundation Colony that provides breeders to all subsequent colonies and including all global partners. This is a way to assure that all animals produced by Taconic and its partners are genetically harmonized.
Outbred Stocks: All outbred stocks originate from a nucleus stock and are bred following Poiley's breeding scheme, Poiley, 1960.
Genetic Testing Program
Taconic currently uses Single Nucleotide Polymorphisms (SNPs) and genotyping in its Genetic Monitoring Program, to monitor genetic background. More specifically, the program uses the Illumina platform and has developed several SNP Panels for Genetic Monitoring of rats and mice, including a C57BL/6 96 SNP Panel to differentiate between C57BL/6N and C57BL/6J substrains and a Rat SNP Panel.
Taconic also uses genotyping through Taqman PCR, qPCR or chip base analysis PCR, and in some cases phenotyping data (Flow Cytometry Analysis) to verify that the pertinent protein is made.
Foundation Colonies: All Foundation colonies are characterized with the 1449 SNP panel. The SNP profile obtained is compared and verified with the line's historical information.
Genetic Monitoring Program: While the colonies are in the barrier and if it is determined that there is genetic risk, for example the same coat color animals are in the barrier, there is in place a genetic monitoring program that tests animals while they are breeding to verify their genetic quality. This testing is performed on a monthly basis and it is reported on our website. The SNP Panel used for this is a 96 SNP Genetics Monitoring panel that distinguishes among all the genetic backgrounds Taconic produces.
Genotyping: In addition to genetic background monitoring, if an inbred strain carries a spontaneous mutation (e.g. Ptprc) the mutation's presence is verified. In many cases the zygosity of the mutation is also monitored.
Genetic Monitoring Program: All of Taconic's outbred stocks are tested at least once a year or if there is genetic risk more often. Taconic's 96 SNP Panel (rat or mouse) is used to monitor the level of heterozygosity of the different colonies and make sure that it is consistent among all production barriers.
Genotyping: In addition to genetic background monitoring if the outbred stock carries a spontaneous mutation, its presence is verified.
Genetically Modified Models
Bringing a New GEM into Taconic: When a new model is brought to Taconic for commercial distribution, all genetic documentation is verified:
Genetic background: SNP profile characterization
Generation number: Historical information of matings including backcrosses and intracrosses
Type of genetic modification: Targeted mutagenesis, CRISPR/CAS 9 modifications and Random Insertion
Adverse phenotypes: History of adverse phenotypes
Colony Breeding: During barrier production the model is mated using the most efficient mating format in order to comply with the 3 Rs (Replacement, Reduction and Refinement) Genotyping and Genetic Background Testing
All GEM models commercially available have a defined SNP profile in order to characterize the genetic background of the model.
Genotyping, includes testing for the mutation, determination of zygosity for the mutation and in some cases the presence of the functional transgene.
Poiley, SM (1960) A systematic method of breeder rotation for non-inbred laboratory animal colonies. Proc Animal Care Panel 10:159-166.