JAX® Mice Genetic Stability Program

Freezing genetic drift in its tracks

"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)

For over 75 years The Jackson Laboratory's genetically defined inbred mice have been the Gold Standard in the field of mouse-based biomedical research. To further ensure the genetic integrity of JAX® Mice we have developed our Genetic Stability Program which is an innovative cryopreservation approach to effectively limit genetic drift.

Why genetic stability is important

Given its impact on human health, the data produced from the ever increasing amount of mouse-based research must be reliable, reproducible, and viable over time and place. It must be conducted with mouse models whose genetic constitutions are as well-defined, stable, and unvarying as possible (Taft et al. 2006). Otherwise, research conclusions may be confounded, inaccurate, misleading, and perhaps unusable. This risk is more than theoretical, as several examples have already been reported: wasted efforts because of a mix-up in AL/N substrains (Bailey, 1982); confounded results due to lack of awareness of 129 substrains (Hogan et al. 1994; Threadgill et al. 1997); dubious results because of inattention to C57BL substrain differences (Specht et al. 2001; Wotjak 2003). How many incidents have not been reported?

How we limit genetic drift

The Jackson Laboratory: pioneer in cryopreservation for over 25 years

The technique of freezing mouse embryos was first reported by Whittingham et al. (1972), and a Cryopreservation Program was launched at JAX in 1976. Since then, The Jackson Laboratory has successfully cryopreserved over 3,600 mouse strains.
To limit genetic drift in our mouse colonies, we use a three-pronged approach:

  • we minimize the number of generations attained in our foundation and production stocks;
  • we use highly skilled and experienced technicians to oversee breeding in those stocks;
  • we have developed a unique Genetic Stability Program*

The Genetic Stability Program (GSP)

GSP was initiated in 2003 and entails cryopreserving supplies of embryos and gametes from a very limited pool of foundation animals from our significant inbred mouse strains. These embryos or gametes are used to refresh our foundation stocks about every five generations. The net result is that there is no accumulation of mutations over time and genetic drift is effectively stopped (Taft et al. 2006).

We have already completed the cryopreservation for the widely used JAX® Mice strains 129S1/SvImJ (002448), C3H/HeJ (000659) C57BL/6J (000664), C57BL/6NJ (005304), DBA/2J (000671), FVB/NJ (001800), NOD/ShiLtJ (001976), and NOD.CB17-Prkdcscid/J (001303), BALB/cByJ (001026), CBA/J (000656) and DBA/1J (000670). Additional strains are continuously added and will be announced as they become available.

Limiting genetic drift in these strains is particularly important because most of the strains currently included in this program have been sequenced: the C57BL/6J strain was sequenced by the Mouse Genome Sequencing Consortium; the sequence for the DBA/2J strain was recently made public by Celera Genomics; and the FVB/NJ, BALB/cByJ, and 13 other JAX® Mice strains have recently been sequenced by the National Institute of Environmental Health Sciences, as part of their 16-strain Resequencing Project. (JAX NOTES 2005, #496).

* based upon patent pending technology

illustration of how our genetic stability program works

A bibliography is available for sources referenced on this page.