Genetic Monitoring Program

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 four strategies:

  1. Visual characteristics of strains (most notably, coat color)
  2. Production procedures that minimize co-localization and/or movement of strains of similar colors and that promote careful record keeping and strain segregation
  3. Standard operating procedures outlining DNA-based marker and/or protein testing of animals at specific, defined, potentially risky points in the production process.
  4. A dedicated new personnel training program and frequent continued training sessions. Taconic's operational personnel are trained in procedures designed to minimize risk for genetic integrity breaks. Personnel are trained to recognize and report potential procedural deviations immediately to eliminate the risk of a genetic integrity break.

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 outbred breeding scheme.

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 2050 SNP Panel that differentiates among the most used inbred strains, a 257 SNP Panel that differentiates among C57BL/6NTac, C57BL/6J and C57BL/6JBomTac substrains, and a rat SNP Panel with over 750 SNP markers that can be used for speed congenic backcrosses in addition to strain background characterization. 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.

Inbred strains:

  • Foundation Colonies: All Foundation colonies are characterized with SNP Panels: 2050 SNP Panel for mice and 759 SNP Panel for rats. The SNP profile obtained is compared and verified with the line's historical information.
  • Genetic Monitoring Program: A genetic monitoring program tests a subset of breeders to verify 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 customized panel analyzed by PCR-based screening of specific SNP and mutation markers that distinguishes among all the genetic backgrounds for which a contamination risk exists at the location. In addition, inbred strains are assessed using the 2050 Illumina SNP panel on a yearly basis.
  • 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.

Outbred stocks:

  • Genetic Monitoring Program: All of Taconic's outbred stocks are tested at least once a year or if there is genetic risk more often. Genetic monitoring SNP Panels for mice and rats (98 SNPs for mice, 96 SNPs for rats) are used to monitor the level of heterozygosity, allele frequencies and inbreeding coefficient of all the SNPs within the different colonies and ensure those parameters are consistent for the various colonies of each outbred line. This monitoring is designed to detect and limit inbreeding of the colony and signal the need to refresh from cryopreserved material.
  • 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
    • Other characteristics

  • 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.

References:
Poiley, SM (1960) A systematic method of breeder rotation for non-inbred laboratory animal colonies. Proc Animal Care Panel 10:159-166.
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