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Differences Among Sublines of Inbred Mouse Strains

Herbert C. Morse III

National Institute of Allergy and Infectious Diseases
National Institutes of Health
Bethesda, Maryland

In many fields other than biology, conclusions reached about comparative results coming from different laboratories are not open to question on the basis of the reagents employed - one organic chemist's supply of toluene is equivalent to another's. It has been an implicit belief among many involved in mouse genetics that a similar constancy is inherent in the use of highly inbred mice for experimental purposes -- one investigator's C3H is equivalent to another's. The elegant theoretical analysis of Bailey ( 1, 2, and this volume) as well as multiple reports of genetic differences among sublines of inbred strains of mice ( 3, 4, 5, 6, 7) clearly demonstrate that this belief is unfounded.

As outlined by Bailey, there are three possible causes for subline differences: 1) contamination from outcrossing, 2) incomplete inbreeding, and 3) mutation. Probable examples of each of these causes are easily found. The demonstration that C57BL/Ks differs from all other C57BL sublines at its entire H-2 complex as well as at least three other histocompatibility loci ( 8) probably reflects unknown outcrossing.

Existing differences among the major sublines of the C3H family -- those of Strong, Bittner, and Andervont -- are undoubtedly due to incomplete inbreeding before distribution. This understanding is based upon Andervont's observation that, on receiving C3H mice from Strong at F15, they were still segregating for coat color. Andervont inbred C3H's, selecting for agouti, for another 17 generations before giving Heston mice in 1942 (H.B. Andervont, personal communication).

Finally, the studies of Flaherty and Rosenstreich (this volume) on Qa antigens and LPS-responsiveness of BALB/c and C3H sublines, respectively, strongly suggest that mutations are responsible for the observed differences in these mice.

In studying the strain differences of XenCSA, a cell-surface antigen related to the major glycoprotein of xenotropic murine leukemia viruses ( Chused and Morse, this volume), we tested several sublines of different inbred strains for expression of this antigen. As shown in Table 1, sublines of C3H, C57BL, and A differ markedly in the amount of XenCSA detected on the surface of thymocytes and spleen cells. High expression of this antigen on lymphoid cells of C57BL/10SnGrf as compared to other C57BL strains probably reflects a mutational event occurring in the relatively recent history of this subline. The basis for other differences among sublines is unknown.

The existence of such genetic differences between sublines of inbred strains can be viewed in two ways. First, they may render results obtained in different laboratories using different sublines of one strain impossible to compare. This could result in a considerable waste of research efforts. On the other hand, detection of differences between closely related sublines provides the equivalent of congenic lines for analyses of gene function. In either case, it is obviously imperative that investigators employing inbred strains provide sufficient information in their papers so that the ancestral relationship of their subline to others can be readily detected. The latter point brings into focus the question of nomenclature. Problems related to appropriate designations of strains, sublines, and genes are dealt with more extensively in the paper by Dr. Lyon which follows.

The remainder of this section is devoted to brief reports of differences detected among sublines of strains C3H, AKR, CBA, C57BL, and BALB/c.


1. Bailey, D.W. (1959). J. Hered. 50: 26.
See also MGI.

2. Bailey, D.W. (1977). Ciba Found. Symp. 52: 291.
See also PubMed.

3. Rechicigl, R., Jr., and Heston, W.E. (1963). J. Natl. Cancer Inst. 30: 855.

4. Acton, R.T., Blankenhorn, E.P., Douglas, T.C., Owen, R.X., Hilgers, J., Hoffman, H.A., and Boyse, E.A. (1973). Nature New Biol. 245: 8.
See also MGI.

5. Maurer, P.H., Merryman, C.F., and Jones, J. (1974). Immunogenetics 1: 398.

6. Taniguchi, M., Tada, T., and Tokuhisa, T. (1976). J. Exp. Med. 144: 20.
See also PubMed.

7. Olsson, M., Lindahl, G., and Ruoslaht, E. (1977). J. Exp. Med. 145: 819.
See also MGI.

8. Graff, R.J. (1970). Transplant. Proc. 2: 15.
See also MGI.

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