Frequently Asked Questions
Question:
What is involved in bringing in a strain for distribution by The Jackson Laboratory? What factors affect the time frame from acceptance to distribution?
Answer:
The process of transferring a strain from a principal investigator’s laboratory to The Jackson Laboratory for distribution is complex. Essentially, three phases are involved: (1) candidate strain submission, review and acceptance; (2) importation, rederivation and genotyping; and (3) colony development, expansion and distribution.
Phase 1: Candidate Strain Submission, Review, and Acceptance
During this phase, investigators interested in donating a new strain submit information on strain characteristics, strain history, breeding performance, and genotyping as well as relevant publications that describe the phenotype and potential research applications. The Genetic Resource Committee at The Jackson Laboratory then reviews the submission and selects specific strains for distribution.
Once a strain has been selected for distribution, The Jackson Laboratory then negotiates any necessary licensing agreements with the originating institution. When all legal issues are resolved, we formally accept the strain. Delays during this phase are primarily due to legal negotiations.
As a final step in phase one, the investigator ships breeder pairs or a few mice to The Jackson Laboratory’s importation facility.
Phase 2: Importation, Rederivation, and Genotyping
Once the mice have been received at The Jackson Laboratory, the mice are transferred into isolators for breeding. Progeny from the original mice sent by the investigator are rederived by either hysterectomy or embryo transfer. The time period required to move mice through this phase depends on the genotype, sex, and number of mice provided as well as the breeding performance and the genotyping method(s) used.
Strains in Phase 2 are categorized as “Under Development - Not Yet Available�. Scientists can register their interest in these strains using a Web-accessible form.
The goal of this phase is to develop a “starter colony� of mice, free of detectable pathogens and with the correct genotype. Prior to moving into the next phase, the starter colony mice must be tested to validate both health status and genotype. Often, genotyping methods must be developed or optimized to confirm the genotype of progeny mice prior to release to breeding colonies. Genotyping methods development can delay release of progeny into the next phase but is absolutely essential in ensuring genetic quality of JAX® Mice.
Other activities that occur during Phase 2 but do NOT delay distribution of the strain
As a standard procedure, we preserve all strains for long term storage by cryopreservation of sperm or embryos. For some selected strains on mixed genetic backgrounds, a few progeny from the starter colonies will be transferred into a backcrossing program to develop congenic strains on stable, inbred genetic backgrounds. The cryopreservation and backcrossing activities are partially supported by the National Institutes of Health and are conducted as services to the research community but do not delay distribution of the strain.
Phase 3: Colony Development, Expansion, and Distribution
Starter colony mice, confirmed as pathogen free and of correct genotype, are then transferred from our importation facility into breeding facilities. During this phase, we optimize strain-specific breeding strategies.
The period of time required to move the strain through this phase depends on the need for developing any specialized husbandry protocols and on the size of a distribution colony needed to meet the anticipated demand. If a large colony is required then the initial progeny are used primarily as breeders to build the colony which can delay distribution by several months. As well, the genotype of mice bred for distribution directly affects the role of colony expansion. Homozygous colonies can be expanded more rapidly than heterozygous colonies.
Once a colony has reached a size to meet anticipated demand and all breeding and quality testing methods are optimized, the strain is released for distribution. Distribution of a new strain is on a first come, first serve basis. Investigators who have registered their interest in a particular strain by contacting our Customer Service Department or by using our on-line new strain interest form are contacted first to allow these individuals to place an order. Following this notification, the new strain will is made publicly available.
Factors Affecting Time Frame
Moving a new strain through these phases typically requires 6 to 12 months. As described above, this process is influenced by several key factors including:
- The legal restrictions imposed by the originating institution and resultant negotiations.
- The genotype, sex, and number of mice originally provided by the investigator.
- The need for methods development, including optimizing a breeding scheme, husbandry protocols, breeding performance, and genotyping.
- Progeny mortality due to severe or lethal mutations.
The Role of Biology
It is important to consider the biology of the mouse throughout this process. Mice are required to go through several generations of breeding during importation, colony development, and expansion. If an “ideal� female mouse (e.g. a standard, easy-to-breed inbred mouse on a defined genetic background) is bred at 6 weeks of age and gives birth by 9 weeks of age, the progeny will be ready for breeding in another 6 weeks.
In the best case scenario, the absolute minimum amount of time to create a starter colony of mice, based on biology alone, is 12 weeks. However, most cases are not ideal, and the original mice sent by investigators usually need to produce several litters to obtain enough mice, of the correct genotype, for a starter colony. Once a starter colony is transferred into a breeding facility, it is likely that these mice will need to undergo additional generations of breeding prior to distribution. The need for additional generations to build a distribution colony typically adds another three to six months to the strain development and expansion time.
New Technologies
Recognizing the fast pace of modern biomedical research, we continually investigate and assess new options and technologies to accelerate the rate of importing and distributing many new strains as quickly as possible.
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