UNC Systems Genetics
In any publication, please refer to the CC animals by their full CCxxx/nnnn nomenclature.
In any publication, please acknowledge the origin of the CC mice used as follows:
For CC strains with the laboratory code “Tau”: Tel Aviv University, Israel1
The strains listed on this page are the CC strains that have reached the following criteria: 1) inbred status: 24 are over 99% and 55 are over 95%, 6 are between 88 and 95% homozygous as of the 2020 MRCAs 2) have 6 to 8 founders, 3) are in SPF or barrier status, 4) will be available from UNC. Some strains are harder to breed than others, so availability may vary. The UNC Systems Genetics Core Facility can provide breeding stock (for internal use unless other permission is acquired) or experimental cohorts. We have attempted to include as much breeding advice as possible, but feel free to contact Rachel Lynch if more advice is desired.
Our goal to give access to all investigators to the CC resource. We have shown that even incipient inbred lines are a powerful genetic resource. Distributing strains that are not 100% inbred addresses the fact that some strains become increasingly difficult to maintain with terminal inbreeding and thus may be lost. Researchers need to carefully evaluate whether the CC strains meet the needs of their experimental design. However, we wish to note that for decades geneticists have used resources with similar shortcomings and that in contrast with these historical resources, users of CC strains will know, with an unprecedented level of detail, which regions are not fixed and what alleles are segregating in these regions.
Rigor and Reproducibility
The SGCF is tasked with providing Collaborative Cross mice to the research community. The CC population is a mouse resource which can be used to assess the impact of genetic variation on various biomedically relevant disease phenotypes.
The SGCF has identified the following variables as those with the potential to most significantly impact the rigor and reproducibility of experiments conducted with this resource.
A. Breeding errors: The SGCF maintains stringent standard operating procedures to reduce the likelihood of breeding errors in the CC colony. However, the possibility remains that two or more strains could be inadvertently crossed. Because many of the CC strains have the same coat color, this can be difficult to identify by external observation. As such, the SGCF has implemented a yearly Quality Control assessment to identify any breeding errors. This is centered on a genotyping survey of the breeding colony with the MiniMUGA (Neogen, Inc) genotyping array. Furthermore, tail snips from all retired breeders are archived for future genomic inquiries.
B. Health status: Currently, the CC colony in the SGCF is split between a Specific Pathogen Free set of strains, and Barrier Facility set of strains. The SGCF has initiated and is continuing the process of standardizing the health status of the Collaborative Cross population it distributes into the higher-health barrier facility via rederivation or reimportation of strains not currently in the barrier facility. Please refer to the website or contact the Core Director for more information regarding the health status.
C. Incomplete inbreeding: The CC strains available at the SGCF are at advanced stages of inbreeding, but most strains are not yet completely inbred. Thus, the SGCF recommends archiving of tissue or DNA from tested animals, and appropriate batching in the design of experiments. The SGCF is committed to making the lines more fully inbred, and concurrently updating relevant genetic information. As such, updated genotypic information, including the inbred status, of the SGCF strains are posted on the website (https://med.sites.unc.edu/sgcf/) and will be updated as part of the annual QC assessment.
D. Reagents and protocols impacted by genetic variation: The CC are a genetically diverse panel of strains. As such, there is a possibility that reagents used in classical inbred studies may not accurately work across the CC. This includes flow cytometry antibodies (e.g. PMID29166619) and molecular assays (e.g. PMID28592495). Note that it has also been observed that widespread and commonly used procedures (e.g. super-ovulation and cryo-recovery protocols) have not been successful in some tested CC strains. Researchers should interface with the SGCF in experimental design to minimize such experimental artefacts.
E. Sex and Batching: While not unique to the CC resource, sex-based differences and batching effects should be taken into account at the experimental design and analysis phases. In general, users should anticipate discussions with the core with regard to rational sample size (more within-strain variability will require more animals per strain); sex-based differences; and expectations with regard to the number of strains to be used to identify genetic differences driving phenotypic responses (information on QTL mapping power in the CC population can be found in the following publication: https://www.biorxiv.org/content/10.1101/459966v3.full). Depending on the phenotype, panels of CC-F1 and/or F2 crosses from CC strains may be more appropriate experimental/mapping populations. The SGCF is prepared to produce such populations for research groups, and consultation with the SGCF is highly encouraged in these experimental designs.
Standard housing/breeding of the CC
Autoclaved and Irradiated ¼″ Bed-o’Cobs by The Andersons Lab Bedding Products (https://andersonslabbedding.com/wp-content/uploads/2012/07/Bed-oCobs_1_4.pdf)
ALPHA-dri® from Shepherd Specialty Papers (http://www.ssponline.com/alpha_dri.htm)
The following strains are housed on Alpha Dri: CC003, CC005, CC007, CC008, CC017, CC025, CC039, CC058, CC065, CC068, CC072, CC079.
Water: Auto water
Feed: LabDiet® Select Verified Rodent Diets 5V0F - Select Rodent 50 IF/6F Auto (https://www.labdiet.com/cs/groups/lolweb/@labdiet/documents/web_content/ndjf/oda0/~edisp/36142_804403.pdf)
Breeder Chow – autoclaved Harlan 2019SX is now LabDiet® Select Verified Rodent Diets 5V0G - Select Rodent 50 IF/9F Auto (https://www.labdiet.com/cs/groups/lolweb/@labdiet/documents/web_content/ndjf/odq5/~edisp/36142_849601.pdf)
The following strains are on Breeder Chow: CC007, CC017, CC021, CC033, CC035, CC039, CC043, CC053, CC061, CC065, CC068, CC072, CC079, CC080.
* designated health status '1' negative for all of the following: by serology - MHV, MVM, NS1, MPV(MPV1, 2, 3), MNV, TMEV, EDIM, Sendai, and Mycoplasma pulmonis. Additionally, some are tested for PVM, Reovirus 3, LCM, Ectromelia, MAD1, MAD2 and Polyoma, by culture nasal swab - Pasteurella pneumotropica, by fecal PCR - Helicobacter
** designated health status '2' negative for all of the following: by serology - EDIM, TMEV GDVII, MHV, Mycoplasma pulmonis, MPV, MVM, Parvo NS-1, PVM, and Sendai. Additionally, some are tested for CAR bacillus, Ectromelia, LCMV, MAD1, MAD2, mCMV, Polyoma, and REO3.