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Standardized Genetic Nomenclature for Mice: Past, Present and Future

Mary F. Lyon

MRC Radiobiology Unit
Harwell, Didcot, Oxon, U.K.

Nomenclature is one of those systems, analogous to digestion, circulation, or respiration, which should function smoothly without our awareness of it. Nevertheless, like those physiological functions it is essential, and since unlike them it is man-made by corporate decisions, it is very important that nomenclature should sometimes be discussed. Perhaps the most convenient way to consider the subject is a historical or developmental sequence.

The history of committees dealing with the nomenclature of mouse genetics and inbred strains has been reviewed by Snell ( 1) and by Staats ( 2) and is presented in tabular form in Table 1. Although inbred strains have been of such paramount importance to mouse genetics and were begun so early in the development of the subject, the first nomenclature committee dealt not with inbred strains but with mouse gene nomenclature. It was formed as early as 1939, when there were only 31 known gene loci and seven linkage groups. This early formation of a nomenclature committee was an important factor in its success since, if nomenclature is allowed to develop in an organized way for any length of time, it becomes very difficult to gain the acceptance of scientists for the changes necessary to produce order. Present day geneticists thus owe a considerable debt to the foresight of those who took part in organizing the first committee. One of the prime movers was G.D. Snell.

Another important factor in the success of any nomenclature committee is the wide dissemination of its findings and in this respect also the first committee made a very wise move in founding the Mouse News Letter, which first appeared in 1949, and is still a major organ today for disseminating information on mouse genetical nomenclature.

Inbred strains as such first entered the nomenclature scene in 1952 when a Committee on Standardized Nomenclature for Inbred Strains of Mice was formed. This group succeeded in gaining wide acceptance not only on the nomenclature for inbred strains, but also on the genetic criteria for the establishment of new inbred strains and for congenic strains, which are now of such great importance and had then recently been introduced, with G.D. Snell again a leading figure. Like the Committee on Gene Nomenclature, the Committee on Inbred Strain Nomenclature attached much importance to the dissemination of its findings and began the listing of inbred strains and their nomenclature in Cancer Research which has been carried out regularly by Joan Staats since then ( 3).

in 1958 the two committees for nomenclature of inbred strains and for gene nomenclature were merged to form the Committee on Standardized Genetic Nomenclature for Mice which is the body responsible for coordinating and regulating all problems concerned with the nomenclature of strains, genes, and chromosome anomalies of the mouse today. The merging of the strain and gene nomenclature committees into a single body was of course highly appropriate, as the contribution of inbred strains, congenic strains, and recombinant strains to knowledge of gene loci has been so great. There were in 1977 approximately 545 gene loci with known variants ( 4), and of these Staats ( 3) listed over 120, or 22%, as being polymorphic in inbred strains.

In 1971 the Committee on Standardized Genetic Nomenclature for Mice (hereafter called the Nomenclature Committee) sought and gained affiliation with the International Committee on Laboratory Animals, which is a dependent body of UNESCP and WHO. Hence, the Nomenclature Committee has official international status. Its members are all scientists working actively in the field. They are drawn from a number of different countries and represent as many areas of expertise in mouse genetics as possible.

The work is carried out largely by correspondence, with occasional meetings timed to coincide with international genetics meetings. When particular problems arise ad hoc subcommittees may be formed to prepare recommendations which are then circulated to scientists active in the area of concern for their comments. Finally the members of the Committee vote on the recommendations ( Table 2).

The present rules for nomenclature fall under three main headings:

  1. Inbred strains (including congenic and recombinant inbred strains).
  2. Gene nomenclature.
  3. Designation of chromosome anomalies.
However, it is clear that knowledge of these three areas is closely interrelated, and one must in fact consider all parts of the nomenclature together ( 5).

From time to time it is necessary to make changes or additions to the rules. In drawing up its suggestions the Committee bears in mind various principles:

  1. The nomenclature must be simple to use.
  2. There should be no ambiguity.
  3. The symbols should convey the maximum information.
  4. The nomenclature must have general acceptance.
  5. The system must be adaptable to future advances in knowledge.

In dealing with simplicity in use, a consideration to be borne in mind is that the symbols should be suitable for use in computerized information retrieval systems, with minimum of modification. Some computers do not handle lower case letters. However, the use of upper and lower case initial letters of gene symbols to indicate dominance or recessivity is standard practice for all organisms ( 8, 9, 10, 11, 12), and more modern computers do handle lower case letters, and hence mouse nomenclature follows the standard practice. On the other hand, subscripts and superscripts are still difficult to handle by computer and hence these are kept to a minimum.

An example of the need to avoid ambiguity lies in the use of substrain symbols for inbred strains. Some of the well known strains have now been inbred for approaching 200 generations. Bailey ( 13) has shown that different branches of these strains may come to differ genetically quite considerably as a result of mutational drift, and with the increasing knowledge of polymorphisms in inbred strains more and more differences among substrains are in fact being found. Thus, it is important that different workers aiming for comparable results should use not only the same strain but the same substrain, and the symbolism should be so devised that it is clear which substrain was used. It is likely that changes will be made in the rules for inbred strain nomenclature in the near future to make the designation of substrains clearer.

A further likely change, aimed at providing maximum information, is in the symbolism for congenic lines. Bailey ( 14) has pioneered the system of including in the name of the strain symbols for both the differential allele(s) and the donor strain which provided the allele, e.g., B10.129-H-12b, a strain with the genetic background of C57BL/10Sn (= B10) but which differs from that strain in a differential allele (H-12b) derived from strain 129/J. This system clearly provides more information than one in which only the donor strain of the differential allele is listed, since if the donor strain is known it may be possible to predict which alleles at neighboring loci have been carried along in the differential chromosomal segment. Consequently, Bailey's nomenclature is likely to be recommended in future.

Conversely, to promote simplicity in use, the inclusion of many details of manipulative processes such as fostering or egg transfer is likely to be discouraged. Obviously, information on such processes is valuable as an indication of the likely presence or absence of vertically transmitted viruses, etc. However, when the original rules were formulated, no one envisaged that strains would be subjected to more than one, or perhaps two, such processes. Now, with the widespread use of fostering in SPF techniques some strains have been fostered many times, and to include such details in the name makes the symbol unwieldy. The advent of freeze preservation as another manipulative process makes the process even worse. Therefore, the Committee is likely to recommend that in future only the most recent manipulative process should be mentioned in the name.

The Committee is of course reluctant to make changes to avoid any risks of confusion and ambiguity, and because frequent changes might not be generally acceptable to scientists. However, the points already mentioned provide examples of the ways in which scientific advances force the need for change.

It may be profitable to try to foresee what changes may be necessary in nomenclature and the work of the Nomenclature Committee in the future. First, one may expect to see a continuing very rapid growth in knowledge of the field. The number of known gene loci in the mouse is showing exponential growth at present, with numbers almost doubling in 10 years ( Figure 1). The number of mapped loci and the numbers of loci known to be polymorphic in inbred strains are likewise increasing very rapidly ( 3, 15).

This means that computer storage of the information on these matters is now essential. It also means much increased work for those who undertake the collection of the information for the Committee. Joan Staats has been the secretary of the Committee and has collected and collated all the information on inbred strains since the first listing in 1952. Tony Searle has been editor of Mouse News Letter, and thereby a collector of information on gene loci since 1969. A great debt is owed to both of them for this work, and perhaps the Committee should consider what might be the difficulties of replacing them if and when they should wish to retire, in view of the ever-increasing work load.

Not only may one expect to see many more known gene loci, but the knowledge of these loci is likely to become far more detailed. There have been reports already of variants which are believed to involve operators, or cis-acting regulators, of structural loci ( 16), and many more of these are likely to be found. Gene complexes, too, will probably need to be incorporated in the nomenclature. At present the H-2 complex is the only well established gene complex ( 17), but there are other possible candidates, such as the closely linked genes Ph, Rw and W on chromosome 5 ( 18).

Knowledge of genetic mapping is also likely to become far more detailed, the location of gene loci relative to chromosomal G-bands will become known, possibly with the aid of polymorphisms of G-bands in inbred strains. This more detailed mapping may mean that in congenic strains, not merely a differential allele, but the full length of the transferred chromosomal segment may be known. Thus, at some time in the future it may be necessary to change the symbolism for congenics once again, to incorporate this information. Certainly the symbols for chromosome anomalies are likely to be changed quite soon to give details of exact positions of chromosome breaks. Yet another possibility is that variants may be found in repetitive DNA, but this point is highly speculative at present ( 19).

The points mentioned so far have concerned mouse genetics sensu stricto, but there are at least two ways in which the Committee is likely to have to broaden its field of interest. On the one hand, there is the question of uniformity of nomenclature among species. There is widespread interest in the evolution and phylogeny of gene loci and, particularly in the case of structural loci for enzymes, homologous loci have been studied not only in mouse, man, and various species of mammals, but also in birds, fish, and insects ( 20, 21, 22, 23). There is obviously a need for liaison among the nomenclature committees for various organisms and possibly the International Genetics Federation could play a role here.

Since the nomenclature of mouse genetics is so well organized, relative to that in some other species, perhaps wider dissemination of the work of the mouse Nomenclature Committee would be valuable. Certainly there is a great need for this wider dissemination of information to those who work with mice but are not geneticists. Genetics is now such a central subject in biology, and the mouse is such a widely used organism, that genetic variants are being used, and new variants are being discovered, in such disparate fields as biochemistry, cancer research, endocrinology, immunology, virology, and so on. Unfortunately many workers in these fields are not fully conversant with genetic terminology, and particularly with mouse genetics nomenclature. Thus, the Nomenclature Committee has an important role in the future, not only in keeping abreast with probable rapid advances in knowledge, but also in disseminating its information as widely as possible in the biological field.


1. Snell, G.D. (1974). Mouse News Letter 50: 7.

2. Staats, J. (1966). In Biology of the Laboratory Mouse, 2nd. Ed. (E.L. Green, ed.), p. 45. McGraw-Hill, New York.

3. Staats, J. (1976). Cancer Res. 36: 4333.
See also MGI.

4. Searle, A.G. (1977). Mouse News Letter 56: 4.

5. Lyon, M.F. (1977). Immunogenetics 5: 393.

6. Committee on Genetic Symbols and Nomenclature (1957). International Union of Biological Sciences Series B No. 30, p. 1.

7. Committee on Standardized Nomenclature for Inbred Strains of Mice (1952). Cancer Res. 12: 602.

8. Committee on Standardized Genetic Nomenclature for Mice (1963). J. Hered. 54: 159.

9. Committee on Standardized Genetic Nomenclature for Mice (1972). J. Hered. 63: 69.

10. Committee on Standardized Genetic Nomenclature for Mice (1973). Biochem. Genet. 9: 369.

11. Committee on Standardized Genetic Nomenclature for Mice (1974). Mouse News Letter 51: 2.

12. Committee on Standardized Genetic Nomenclature for Mice. (1976). Mouse News Letter 54: 2.

13. Bailey, D.W., (1978). In Origins of Inbred Mice (H.C. Morse III, ed.). Academic Press, New York.

14. Bailey, D.W. (1977). Inbred Strains of Mice 10: 26.

15. Roderick, T.H., and Davisson, M.T. (1977). Ann. Rep. Jackson Lab. 48: 49.

16. Paigen, K., Swank, R.T., Tomino, S., and Ganschow, R.E. (1975). J. Cell Physiol. 85: 379.
See also MGI.

17. Klein, J., Bach, F.H., Festenstein, F., McDevitt, H.O., Shreffler, D.C., Snell, G.D., and Stimpfling, J.H. (1974). Immunogenetics 1: 184.

18. Searle, A.G., and Truslove, G.M. (1970). Genet. Res. 15: 227.
See also MGI.

19. Lyon, M.F., and Mason, I. (1977). Genet. Res. 29: 255.

20. Harris, H. (1975). The Principles of Human Biochemical Genetics, 2nd Ed. North Holland, Amsterdam.

21. Lush, I.E. (1966). The Biochemical Genetics of Vertebrates Except Man. North Holland, Amsterdam.

22. Masters, C.J., and Holmes, R.S. (1972). Biol. Rev. 47: 309.
See also PubMed.

23. Courtright, J.B. (1976). Adv. Genet. 18: 249.
See also PubMed.

24. Dunn, L.C., Grüneberg, H., and Snell, G.D. (1940). J. Hered. 31: 505.

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