JAX® Patents Unique Genetic Stability Program
September 22, 2009
"This insidious evolution of the inbred genotype is known as genetic drift. It is capable of subverting the conclusions reached about comparable research results coming from different laboratories when each uses its own subline of the same inbred strain" (Bailey 1977).
Will your mouse-based research stand the test of time? Or will it be confounded by genetic drift, ". . . the constant tendency of genes to evolve even in the absence of selective forces . . . fueled by spontaneous neutral mutations that disappear or become fixed in a population at random" (Silver 1995)? Until recently, researchers have had limited control over genetic drift in laboratory mouse strains. Hence, they've had little guarantee that the genetic make-up of a laboratory mouse strain hasn't or won't change. This may be particularly troublesome in light of the recent discoveries that copy number variations (CNVs) are ubiquitous in many organisms (including humans and mice) and account for a significant and previously unsuspected genome-changing dynamic (JAX®NOTES 2009). As early as the 1970s Whittingham (1974) and Bailey (1977), a Jackson Laboratory scientist, anticipated this problem and discussed the possibility of using cryopreservation to limit genetic drift in inbred mouse strains. JAX scientist Dr. Mobraaten discussed the possibility again in 1986 (Mobraaten 1986). In 2003, JAX scientists Drs. Wiles, Eicher, and Taft devised and implemented a viable strategy for effectively stopping cumulative genetic drift in inbred mouse strains (Taft et al. 2006). Their method has since been the basis of JAX's unique Genetic Stability Program (GSP) and is now protected by US patent 7,592,501, Methods for Maintaining Genetic Stability of Inbred Animal Strains.
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JAX scientists Drs. Wiles, Eicher, and Taft (left to right) devised and implemented the technology that has since become the basis of JAX's GSP. | ||
JAX's GSP
JAX's GSP is the only one of its kind. It literally freezes genetic drift in its tracks in the most popular JAX® Mice strains by refreshing foundation stocks with cryopreserved pedigree embryos or gametes approximately every five generations. So far, by using assisted reproductive technologies with mice that span only two or three generations, JAX has produced and cryopreserved approximately 25-year supplies of gametes and embryos from the following commonly used strains:
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| The JAX® GSP. Foundation stocks of widely used strains are refreshed with cryorecovered embryos about every five generations. |
Limiting genetic drift in these strains is particularly important because they have been extensively sequenced: The C57BL/6J strain was completely sequenced by the Mouse Genome Sequencing Consortium (Waterston et al. 2002); the DBA/2J strain was partly sequenced by Celera Genomics (Marshall 2001); and sequences for the NOD/ShiLtJ, C3H/HeJ, C57BL/6NJ and 12 other JAX® Mice strains will be available soon from the Sanger Institute Mouse Genomes Project (www.sanger.ac.uk/modelorgs/mousegenomes).
We are continually expanding our GSP program by cryopreserving the germplasm of additional inbred strains each year. In the very near future, we will be cryopreserving germplasm from inbred strain C57BL/10J (000665).
Do Your Part to Lessen the Impact of Genetic Drift (and Genetic Contamination)
You can lessen the impact of genetic change on mouse-based biomedical research by practicing the following:
- Obtain mice from a reliable breeding source, preferably one with a GSP and good genetic quality assurance
- If you maintain your own private colonies of inbred mice, periodically (every 5-10 generations) obtain new breeding stocks from your supplier
- Although colonies of inbred mice expanded from JAX breeding stock can be maintained either by sibling or non-sibling matings, they are technically substrains if they are expanded beyond 10 generations
- Take care when comparing results among substrains: those that arose earlier in a strain's inbreeding regimen or that have been long separated may be genetically different
- Use proper nomenclature to describe your mouse models in your mouse colony and especially in publications
- Include a detailed description of the genetic background and environmental housing conditions of the mice you use in all your research communications
- When possible, use a well-defined genetic background so that your experiments can be replicated
Put time on your side. Use JAX® Mice - dependable, consistent quality, and genetically well-defined.
More information about our genetic quality and stability programs
Read the press release regarding this new patent
References
(Authors in bold are/were Jackson Laboratory scientists.)
Bailey DW. 1977. Genetic drift: the problem and its possible solution by frozen-embryo storage. Ciba Found Symp 291-303.
JAX® NOTES. 2009. Copy number variations (CNVs): a new level of genomic complexity revealed. JAX® Notes 513:5-6.
Marshall E. 2001. Genome sequencing. Celera assembles mouse genome; public labs plan new strategy. Science 292:822.
Mobraaten LE. 1986. Mouse embryo cryobanking. J In Vitro Fert Embryo Transf 3:28-32.
Silver L. 1995. Mouse Genetics. Oxford. p 394.
Taft RA, Davisson M, Wiles MV. 2006. Know thy mouse. Trends Genet 22:649-53.
Waterston RH et al. 2002. Initial sequencing and comparative analysis of the mouse genome. Nature 420:520-62.
