Lab Anim Res.  2017 Jun;33(2):119-123. 10.5625/lar.2017.33.2.119.

Use of C57BL/6N mice on the variety of immunological researches

• Song HK
• Hwang DY

• KMID: 2407425
• DOI: http://doi.org/10.5625/lar.2017.33.2.119

Abstract

Inbred mice are an essential animal strain for research as they can improve the reproducibility and reliability of study results. The establishment of new inbred lines is continuing, and new inbred lines are being used in many research fields. C57BL/6 is a mouse laboratory animal that has been developed and used as an inbred strain since early stage of mouse strain development, and, in the 1950s, C57BL/6 was separated into substrains by the Jackson Laboratory (C57BL/6J) and the National Institutes of Health (C57BL/6N). C57BL/6 mice have been used in immunology and antitumor activity studies since the early strain development stage. After the mouse genome was fully described, C57BL/6 mice use in many areas of research has expanded. In particular, immunological characteristics such as those related to cell-mediated immunity and NK cell activity are relatively higher in C57BL/6 mice than in other mice. The C57BL/6NKorl is a stock of C57BL/6N established as part of a localization of experimental animal strategy of the Korean Food and Drug Administration. Based on analysis of single nucleotide polymorphisms (SNPs), C57BL/6NKorl is considered a genetically distinct inbred stock from other C57BL/6N. Various research efforts have been made to describe the characteristics and increase knowledge of the characteristics of C57BL/6Nkorl. The results obtained through these efforts are expected to increase the utilization of C57BL/6Nkorl as a domestic laboratory animal resource and to enhance the reliability of mouse based studies.

Keyword

C57BL/6N; C57BL/6NKorl; inbred strain; laboratory animal resources

MeSH Terms

Allergy and Immunology
Animals
Animals, Laboratory
Genome
Immunity, Cellular
Killer Cells, Natural
Mice*
National Institutes of Health (U.S.)
Polymorphism, Single Nucleotide
United States Food and Drug Administration

Figure

• 

  Figure 1 History of C57BL/6 substrain. C.C. Little established C57BL in 1921. C57BL/6 was isolated in 1937 and maintained in Jackson Laboratories (6J). C57BL/6N was isolated from Jackson Laboratories mice in 1951 and maintained by the NIH. Subsequently, the C57BL/6N strain moved to commercial companies, such as Charles River Laboratory, Harlan Sprague Dawley and Taconic Farms [20].

• 

  Figure 2 PCA (Principal component analysis) analysis was performed based on the results of 100 SNPs of 48 mice (12 per group). Use HelixTree SVS8 software for PCA analysis. Input the sample-specific genotype as an input file and calculate the vector that best separates the principal component. The most significant Eisen values 1 and 2 are plotted as PC1 and PC2, respectively. PCA analysis showed that C57BL/6NTac and C57BL/6NKorl form independent clusters, but C57BL/6NCrl and C57BL/6NHsd have the same genetic characteristics. Even in the same sample group, C57BL/6NKorl and C57BL/6NHsd have only the same genotype and Spot is not distinguished. C57BL/6NCrl and C57BL/6NTac have some genetic differences in the sample group [36].

Reference

1. Festing MF. Properties of inbred strains and outbred stocks, with special reference to toxicity testing. J Toxicol Environ Health. 1979; 5(1):53–68. PMID: 423306.

2. WRIGHT S. The genetics of vital characters of the guinea pig. J Cell Comp Physiol. 1960; 56(Suppl 1):123–151.

3. Wade CM, Daly MJ. Genetic variation in laboratory mice. Nat Genet. 2005; 37(11):1175–1180. PMID: 16254563.

4. Barros SF, Friedlanskaia I, Petricevich VL, Kipnis TL. Local inflammation, lethality and cytokine release in mice injected with Bothrops atrox venom. Mediators Inflamm. 1998; 7(5):339–346. PMID: 9883969.

5. Crawley JN, Belknap JK, Collins A, Crabbe JC, Frankel W, Henderson N, Hitzemann RJ, Maxson SC, Miner LL, Silva AJ, Wehner JM, Wynshaw-Boris A, Paylor R. Behavioral phenotypes of inbred mouse strains: implications and recommendations for molecular studies. Psychopharmacology (Berl). 1997; 132(2):107–124. PMID: 9266608.

6. Harris RB, Mitchell TD, Yan X, Simpson JS, Redmann SM Jr. Metabolic responses to leptin in obese db/db mice are strain dependent. Am J Physiol Regul Integr Comp Physiol. 2001; 281(1):R115–R132. PMID: 11404285.

7. Kile BT, Mason-Garrison CL, Justice MJ. Sex and strain-related differences in the peripheral blood cell values of inbred mouse strains. Mamm Genome. 2003; 14(1):81–85. PMID: 12532271.

8. Madiehe AM, Hebert S, Mitchell TD, Harris RB. Strain-dependent stimulation of growth in leptin-treated obese db/db mice. Endocrinology. 2002; 143(10):3875–3883. PMID: 12239099.

9. Nishina PM, Wang J, Toyofuku W, Kuypers FA, Ishida BY, Paigen B. Atherosclerosis and plasma and liver lipids in nine inbred strains of mice. Lipids. 1993; 28(7):599–605. PMID: 8355588.

10. Opsahl ML, McClenaghan M, Springbett A, Reid S, Lathe R, Colman A, Whitelaw CB. Multiple effects of genetic background on variegated transgene expression in mice. Genetics. 2002; 160(3):1107–1112. PMID: 11901126.

11. Rossmeisl M, Rim JS, Koza RA, Kozak LP. Variation in type 2 diabetes--related traits in mouse strains susceptible to diet-induced obesity. Diabetes. 2003; 52(8):1958–1966. PMID: 12882911.

12. Sellers RS, Clifford CB, Treuting PM, Brayton C. Immunological variation between inbred laboratory mouse strains: points to consider in phenotyping genetically immunomodified mice. Vet Pathol. 2012; 49(1):32–43. PMID: 22135019.

13. van Bogaert MJ, Groenink L, Oosting RS, Westphal KG, van der Gugten J, Olivier B. Mouse strain differences in autonomic responses to stress. Genes Brain Behav. 2006; 5(2):139–149. PMID: 16507005.

14. Woodworth CD, Michael E, Smith L, Vijayachandra K, Glick A, Hennings H, Yuspa SH. Strain-dependent differences in malignant conversion of mouse skin tumors is an inherent property of the epidermal keratinocyte. Carcinogenesis. 2004; 25(9):1771–1778. PMID: 15105299.

15. Green MC, Grueneberg H, Hertwig P, Heston WE, Lyon MF, Medvedev NN, Snell GD, Staats J. A revision of the standardized genetic nomenclature for mice. J Hered. 1963; 54:159–162. PMID: 14057864.

16. Silver LM. Mouse genetics: concepts and applications. New York: Oxford University Press;1995. p. 3–31.

17. Dux A, Mhlbock O, Bailey DW. Genetic analyses of differences in incidence of mammary tumors and reticulum cell neoplasms with the use of recombinant inbred lines of mice. J Natl Cancer Inst. 1978; 61(4):1125–1129. PMID: 212568.

18. Eppig JT, Blake JA, Bult CJ, Kadin JA, Richardson JE. Mouse Genome Database Group. The mouse genome database (MGD): new features facilitating a model system. Nucleic Acids Res. 2007; 35(Database issue):D630–D637. PMID: 17135206.

19. Mekada K, Abe K, Murakami A, Nakamura S, Nakata H, Moriwaki K, Obata Y, Yoshiki A. Genetic differences among C57BL/6 substrains. Exp Anim. 2009; 58(2):141–149. PMID: 19448337.

20. Zurita E, Chagoyen M, Cantero M, Alonso R, Gonzlez-Neira A, Lpez-Jimnez A, Lpez-Moreno JA, Landel CP, Bentez J, Pazos F, Montoliu L. Genetic polymorphisms among C57BL/6 mouse inbred strains. Transgenic Res. 2011; 20(3):481–489. PMID: 20506040.

21. Derhovanessian E, Solana R, Larbi A, Pawelec G. Immunity, ageing and cancer. Immun Ageing. 2008; 5:11. PMID: 18816370.

22. McVicar DW, Winkler-Pickett R, Taylor LS, Makrigiannis A, Bennett M, Anderson SK, Ortaldo JR. Aberrant DAP12 signaling in the 129 strain of mice: implications for the analysis of gene-targeted mice. J Immunol. 2002; 169(4):1721–1728. PMID: 12165492.

23. Malhotra A, Shanker A. NK cells: immune cross-talk and therapeutic implications. Immunotherapy. 2011; 3(10):1143–1166. PMID: 21995569.

24. Mayer A, Lilly F, Duran-Reynals ML. Genetically dominant resistance in mice to 3-methylcholanthrene-induced lymphoma. Proc Natl Acad Sci U S A. 1980; 77(5):2960–2963. PMID: 6930679.

25. Waldhauer I, Steinle A. NK cells and cancer immunosurveillance. Oncogene. 2008; 27(45):5932–5943. PMID: 18836474.

26. Talmadge JE, Meyers KM, Prieur DJ, Starkey JR. Role of natural killer cells in tumor growth and metastasis: C57BL/6 normal and beige mice. J Natl Cancer Inst. 1980; 65(5):929–935. PMID: 6933263.

27. Corbett AJ, Coudert JD, Forbes CA, Scalzo AA. Functional consequences of natural sequence variation of murine cytomegalovirus m157 for Ly49 receptor specificity and NK cell activation. J Immunol. 2011; 186(3):1713–1722. PMID: 21187440.

28. Dokun AO, Kim S, Smith HR, Kang HS, Chu DT, Yokoyama WM. Specific and nonspecific NK cell activation during virus infection. Nat Immunol. 2001; 2(10):951–956. PMID: 11550009.

29. Boehm T. Design principles of adaptive immune systems. Nat Rev Immunol. 2011; 11(5):307–317. PMID: 21475308.

30. Chen J, Flurkey K, Harrison DE. A reduced peripheral blood CD4(+) lymphocyte proportion is a consistent ageing phenotype. Mech Ageing Dev. 2002; 123(2-3):145–153. PMID: 11718808.

31. Chen J, Harrison DE. Quantitative trait loci regulating relative lymphocyte proportions in mouse peripheral blood. Blood. 2002; 99(2):561–566. PMID: 11781239.

32. Glineur S, Antoine-Moussiaux N, Michaux C, Desmecht D. Immune depression of the SJL/J mouse, a radioresistant and immunologically atypical inbred strain. Immunobiology. 2011; 216(1-2):213–217. PMID: 20965099.

33. Karamitros D, Kotantaki P, Lygerou Z, Kioussis D, Taraviras S. T cell proliferation and homeostasis: an emerging role for the cell cycle inhibitor geminin. Crit Rev Immunol. 2011; 31(3):209–231. PMID: 21740351.

34. Pepper M, Jenkins MK. Origins of CD4(+) effector and central memory T cells. Nat Immunol. 2011; 12(6):467–471. PMID: 21739668.

35. Mills CD, Kincaid K, Alt JM, Heilman MJ, Hill AM. M-1/M-2 macrophages and the Th1/Th2 paradigm. J Immunol. 2000; 164(12):6166–6173. PMID: 10843666.

36. Ministry of Food and Drug Safety. Establishement for the stock of the domestic laboratory animals. Annu Rep 2015.