Taconic Biosciences Product Highlight - The Knockout Mouse Repository (KOR)

Kenneth Platt, PhD
Friday, June 26th, 2015
The Taconic Biosciences Knockout Mouse Repository's more than 4,100 lines provide academic and commercial researchers worldwide with unparalleled access to fully licensed knockout mouse models. This repository offers the scientific community immediate access to expertly derived, highly valuable research tools that rapidly accelerate translational research and the drug discovery and development processes. Eliminating the time associated with the design and development of these mouse models provides a tremendous competitive advantage.

The knockout mouse lines comprising this repository were generated by Lexicon Pharmaceuticals Incorporated using the gold standard of genetic alteration methodology; embryonic stem (ES) cell technology. Mutations were focused on the ‘druggable’ gene classes and were generated using two complementary, proven technologies: Gene Targeting and Gene Trapping.

complimentary approaches to knocking-out the druggable genome

The KOR lines are stored as cryopreserved materials. Heterozygous cohorts can typically be produced and delivered to the customer within 14-16 weeks of order receipt. For most lines, the mouse ES cells used to generate the model are derived from the 129S5 strain. Lines are stored primarily as cryopreserved sperm on a mixed 129S5 x C57BL/6JTyrc-Brd background. Lines are typically recovered using cryopreserved sperm and C57BL/6NTac oocyte donors. Some lines are stored as cryopreserved embryos and when revitalized will result in a 129/S5 x C57BL/6JTyrc-Brd background. For standard orders, clients will receive a minimum of four (4) mutant mice, heterozygous for the selected mutation, including at least one (1) breeding pair on a mixed 129S5;B6 background, validated genotyping protocols, comprehensive genetic report, and animal health data.

Using the KOR to advance research

The KOR represents a highly valuable research tool for researchers interested in understanding gene function in the context of the whole animal. This collection is especially useful to scientists interested in functional genomics as part of a drug discovery program (refs. 1-3). As the KOR contains over 4,100 individual gene mutations, those looking for a specific gene knockout model will likely have success searching the KOR web page.

There are many reasons the KOR might represent the perfect solution to your research needs.

  1. Reliability - The mutations found within the repository are very well defined and difficult to duplicate using gene editing techniques. The targeted mutations were expertly designed to disrupt important protein coding domains and have been confirmed by precise molecular techniques.
  2. Characterization - All the KOR lines have been phenotyped. This initial characterization gives insight into the effects of the mutation including viability and fertility in the homozygous animals. This viability and fertility data can be made available before an order is placed. A comprehensive genetic information package is provided with each order. There are publications supporting many of the lines as well.
  3. Speed - The KOR lines are recovered from frozen sperm or embryos allowing researchers to quickly gain access to heterozygous breeding pairs typically in 14 weeks. Relative to generating the mutation from scratch, this saves considerable time and cost associated with the design, generation, transmission, and maintenance of the mutant line.
  4. Full use rights - Access to the KOR lines come with very simple terms. Customers may breed, cross breed, and perform studies without the need to obtain additional rights to use. This keeps the actual cost per animal reasonable. The rights are granted in the initial license and there are no renewal fees.
Taconic Biosciences’ Knockout Repository represents a premier research tool for in vivo genetic studies. Customers accessing this rich repository can advance their research to the next level. Taking advantage of Taconic’s expertise in other areas such as breeding and novel model generation can reduce the burden on the research program and also allow cutting edge genetic research (e.g. analysis of models with multiple gene mutations).

References:
1. Curr Opin Pharmacol. 2003 Oct;3(5):563-70. Predicting drug efficacy: knockouts model pipeline drugs of the pharmaceutical industry. Zambrowicz BP, Turner CA, Sands AT.
2. Nat Rev Drug Discov. 2003 Jan;2(1):38-51. Knockouts model the 100 best-selling drugs--will they model the next 100? Zambrowicz BP, Sands AT.
3. Trends Biotechnol. 2002 Jan;20(1):36-42. Full-speed mammalian genetics: in vivo target validation in the drug discovery process. Abuin A1, Holt KH, Platt KA, Sands AT, Zambrowicz BP.

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