Agenda

Having a genetic monitoring program is critical when breeding mice in a colony. For inbred colonies, routine monitoring of the genetic background of the strain is essential to maintain and assess the genetic integrity of the colony while reducing and controlling genetic variability. However, for outbred colonies, the primary objective is to maintain a maximum amount of genetic variability within this colony. Discussion included establishment of genetic monitoring programs, use of different technologies/assays used for genetic monitoring, genetic contamination due to mis-mating, genetic drift or incomplete backcrossing and the problems associated with closed colonies of outbreds. Participants learned about the need for a genetic monitoring program in their own colonies, the need to establish a schedule for genetic monitoring so that this is done with reasonable frequency, and how to integrate genetic monitoring into a breeding program.

More about Dr. Ana Perez

Dr. Perez is responsible for defining Taconic's genetic corporate policies and for ensuring the genetic integrity of all animals produced at all Taconic sites in addition of Taconic global distributors. She oversees Taconic's global Genetic Monitoring Program and breeding programs to ensure the preservation of genetic quality.

Dr. Perez has previous experience in generating genetically modified mouse models with several different platforms such as conditional and classical knockout, knock in, classical transgenesis, etc. She also has extensive experience in complex breeding of mouse and rat mutant models including phenotypic characterization of such models.

Download the presentation slides.

Webinar Questions and Answers

Q: How to keep the genetic background stable for lines that carry 6 to 8 genetic modifications?
A: For this case, the modified models can be backcrossed every so often to the inbred strain and of course cryopreserving the strain will do the trick.

Q: Do you have a protocol you use for when to test a colony for genetic drift using SNP analysis?
A: It is best to test a colony at least yearly to check for any unexpected problems on the background strain but remember the best practice for genetic drift is cryopreservation.

Q: In a colony, how often should you replace your breeder pairs to minimize genetic drift?
A: To avoid genetic drift, Taconic would recommend replacing the breeders at most every 2 years.

Q: How many generations can we breed a mouse strain prior to replenishing the stock?
A: Taconic would suggest 4 generations.

Q: We have had a mutant mouse colony with about 4 breeder pairs for the last 8 years, and over the last year have started finding different results. Is it possible that a mutation got fixed in all 4 breeder pairs?
A: We would need more details on the particular breeder information and type of mutation to be able to assess this situation. If we are talking about 4 breeder pairs that are saved and mated randomly, indeed it is possible to fix the mutation.

Q: I understand there is a way to target transgenes using the Rosa locus. Can you talk about that?
A: The ROSA locus is being targeted to drive transgenes we call it Targeted Transgenesis. With this technology there are two important things. First you assure consistent expression of the transgene because the ROSA locus is a strong promoter and in addition a single copy of the transgene is introduced therefore the copy number variable is better controlled.

Q: If I want to cryopreserve my mutant mouse, what is the best time to do this?
A: The best time to cryopreserve your mutant mouse is once you have it in the desired genetic background.

Q: If the strain name says B6, one can't know which C57BL/6 substrain, right?
A: Correct, unless the substrain is specified in the history of the generation of the mutant you would not know. In addition, in many cases you could have a mix of B6 substrains.

Q: What steps are you taking to prevent genetic drift in your conventionally available models such as outbred nudes?
A: For outbreds we do yearly genetic monitoring of our colonies to make sure that the allelic heterogeneity is preserved. We also have frozen stocks of our outbred stocks.