In 2001, the International Committee on Standardized Nomenclature for Mice and the Rat Genome and Nomenclature Committee agreed to establish a joint set of rules for strain nomenclature, applicable to strains of both species. These rewritten guidelines reflect this collaboration, in addition to documenting new and revised rules for the naming of strains. This document is updated annually by the international nomenclature committees for mouse and rat.
Reference to former versions of the rules for mouse strain nomenclature can be found in Snell (1941), Committee for Standardized Genetic Nomenclature in Mice (1952, 1960, 1976, 1981, 1989, 1996), Festing (1979, 1993), Staats (1986), Maltais et al. (1997). A recent summary of mouse guidelines was published in 2006 (Eppig 2006). Reference to former rules for rat strain nomenclature can be found in Committee on Rat Nomenclature (1992).
Current nomenclature rules for naming genes are available online at:
1.1 Mice
1.2 Rats
2. Laboratory codes
3. Inbred Strains and Hybrids
3.1 Definition
3.2 Nomenclature of Inbred Strains
3.3 Indication of Inbreeding
3.4 Substrains
3.5 Hybrids
4. Strains Made from Multiple Inbred Strains
4.1 Recombinant Inbred Strains
4.2 Mixed Inbred Strains
4.3 Recombinant Congenic Strains
4.4 Advanced Intercross Lines
5. Coisogenic, Congenic, and Segregating Inbred Strains
5.1 Coisogenic Strains
5.2 Congenic Strains
5.3 Chromosome Substitution or Consomic Strains
5.3.1 Consomic Strains
5.4 Segregating Inbred Strains
5.5 Conplastic Strains
6. Outbreds and Closed Colonies
6.1 Outbreds
6.2 Closed Colonies
7. References
Mice and rats used in the laboratory derive from a variety of sources. Production of inbred strains means that these backgrounds can be defined and thus require nomenclature conventions. It should be borne in mind that genetic drift means that there may still be unknown genetic differences between individuals within strains.
Most laboratory mice have contributions from both Mus musculus musculus and Mus musculus domesticus. There is evidence that smaller contributions also may have come from Mus musculus molossinus and Mus musculus castaneus. Therefore, they should not be referred to by species name, but rather as laboratory mice or by use of a specific strain or stock name. (In addition, some recently developed laboratory mouse strains are derived wholly from other Mus species or other subspecies, such as M. spretus).
Mouse strain names should be registered through the Mouse Genome Database (MGD) at http://www.informatics.jax.org/mgihome/submissions/amsp_submission.cgi.
Laboratory rat strains derive from the Rattus norvegicus species. Another species, Rattus rattus, also is used as an experimental model, but has not contributed to the common laboratory rat strains.
Rat strain names should be registered through the Rat Genome Database (RGD) at http://rgd.mcw.edu.
A key feature of mouse and rat nomenclature is the Laboratory Registration Code or Laboratory code, which is a code of usually three to four letters (first letter uppercase, followed by all lowercase) that identifies a particular institute, laboratory, or investigator that produced, and may hold stocks of, a mouse or rat strain. Substrains should be identified by Laboratory codes, as should congenic and other strains where several different forms exist that are not otherwise distinguishable. Laboratory codes are assigned by the Institute of Laboratory Animal Research (ILAR) (http://dels-old.nas.edu/ilar_n/ilarhome/register_lc.php).
Examples of Laboratory codes are:
J The Jackson Laboratory Rl W.L. and L.B. Russell Jr John Rapp Mcw Medical College of Wisconsin Kyo Kyoto University
Strains can be termed inbred if they have been mated brother x sister for 20 or more consecutive generations, and individuals of the strain can be traced to a single ancestral pair at the 20th or subsequent generation. At this point the individuals' genomes will on average have only 0.01 residual heterozygosity (excluding any genetic drift) and can be regarded for most purposes as genetically identical. Inbred strains must be continuously mated brother x sister (or equivalent) thereafter.
Other breeding schemes can be used to produce inbred strains; consecutive parent x offspring mating may be used, provided that the younger of the parents is always used (i.e., the offspring that is mated to parent is subsequently mated to its offspring). Other breeding schemes are acceptable provided that the inbreeding is equivalent to 20 successive generations of sib mating (Green 1981).
An inbred strain should be designated by a unique brief symbol made up of uppercase, Roman, letters, or a combination of letters and numbers beginning with a letter. (Note that some pre-existing strains do not follow this convention; e.g., mouse strain 129P1/J).
Care should be taken that mouse and rat strains do not overlap in strain designations. (Note: a few historical examples exist of similar mouse and rat strain designations and these are allowed to stand, with their substrain designations identifying them as unique).
Inbred strains that have a common origin, but are separated before F20 are related inbred strains, and symbols should reflect this relationship.
Examples:
3.3 Indication of Inbreeding
Mouse strains: NZB, NZC, NZO Rat strains: SR, SS
The number of brother x sister inbreeding generations can be indicated, if necessary, by addition in parentheses of F followed by the number of generations.
Example:
Rat strain: ACI/N (F159)
If there is not information as to the total number of generations, but a minimum number of recent inbreeding generations is known, this can be shown by a question mark + the known number of subsequent generations of inbreeding.
Example:
Mouse strain: C3H/HeJ-ruf (F?+25)
Established inbred strains may genetically diverge with time into substrains, due to a number of circumstances:
Substrains are given the root symbol of the original strain, followed by a forward slash and a substrain designation. The designation is usually the Laboratory code of the individual or laboratory originating the strain.
Examples:
IS/Kyo Substrain of IS rat strain originating at Kyoto University. A/He Substrain of A mouse strain originating from Walter Heston.
If a laboratory originates more than one substrain, serial numbers should be added to the Laboratory code.
Example:
Mouse strains: FL/1Re, FL/2Re
(Note that historical exceptions to this rule exist; for example, in mouse, BALB/c is not a substrain, DBA/1 and DBA/2 are separate strains and are not substrains.)
Substrains may give rise to further substrains by continued maintenance by a different investigator or through establishment of a new colony. In addition, substrains arise if demonstrable genetic differences from the original substrain are discovered. In either case, further substrain designations are added, without the addition of another slash.
Examples:
C3H/HeH Mouse substrain derived at Harwell (H) from the Heston (He) substrain of C3H. SR/JrIpcv Rat substrain derived at Institute of Physiology, Czech Academy of Sciences (Ipcv) from the John Rapp (Jr) substrain of SR
Laboratory codes should be accumulated because genetic differences will accumulate with time, the rate depending to some extent on varying levels of quality control at the facilities that have housed and bred the strain or substrain. Organizations distributing mice and rats should include the number of generations the strain has been separated from the parent strain in the information they provide regarding the strain. Strain names can be abbreviated in publications after the first mention of the full proper designation.
Mice or rats that are the progeny of two inbred strains, crossed in the same direction, are genetically identical, and can be designated using uppercase abbreviations of the two parents (maternal strain listed first), followed by F1. Note that reciprocal F1 hybrids are not genetically identical, and their designations are, therefore, different.
Examples:
D2B6F1 Mouse that is the offspring of a DBA/2 mother and C57BL6/J father. A full F1 designation is (DBA/2N x C57BL/6J)F1. B6D2F1 Mouse that is the offspring of the reciprocal cross. A full F1 designation is (C57BL/6J x DBA/2N)F1. CB1BD22F1 Mouse that is the offspring of two recombinant inbred strains, a CXB1 mother and BXD22 father; full F1 designation is(CXB1/ByJ x BXD22/TyJ)F1.
Further crosses produce offspring that are no longer genetically identical, but it may still be appropriate to give them designations reflecting their parentage, similar to those for F1 hybrids.
Examples:
D2B6F2 are offspring of a D2B6F1 intercross. B6(D2AKRF1) are offspring of a (DBA/2 x AKR/J)F1 male backcrossed to a C57BL/6J female.
In all the above cases, for clarity, the full strain symbols should be given in any publication when the hybrids or crosses are first referred to. If a hybrid is constructed using a substrain known to differ from the "standard" strain genetically and/or phenotypically, the substrain should be indicated in the hybrid symbol; e.g., BALB/cBy = CBy, C3H/HeSn = C3Sn.
Approved abbreviations for common mouse strains are listed below:
129
129 strains (may include subtype, e.g., 129S6 for strain 129S6/SvEvTac) A
A strains AK
AKR strains B
C57BL B6
C57BL/6 strains B10
C57BL/10 strains BR
C57BR/CD C
BALB/c strains C3
C3H strains CB
CBA D1
DBA/1 strains D2
DBA/2 strains HR
HRS/J L
C57L/J R3
RIIIS/J J
SJL SW
SWR
Mice or rats can be produced that have a defined genetic background, derived from two or more inbred strains, and that may or may not be genetically identical. Such animals should be designated appropriately, according to the breeding scheme that produced them.
Recombinant inbred (RI) strains contain unique, approximately equal proportions of genetic contributions from two original progenitor inbred strains. Traditionally, recombinant inbred (RI) strains are formed by crossing animals of two inbred strains, followed by 20 or more consecutive generations of brother x sister matings (Bailey 1971, Taylor 1978). Alternate breeding schemes can be used, such as creating RI strain sets from Advanced Intercross Lines, where F2 animals are nonsib mated for several generations, followed ultimately by 20 or more consecutive generations of brother x sister matings. Note that if backcrossing to one of the parental strains is involved, this will create recombinant congenic strains and should be named accordingly. RI strains should be designated by uppercase one- or two-letter abbreviations of both parental strain names, with the female strain written first, and separated by an uppercase letter X with no intervening spaces. All members of RI sets involving the same two strains will be serially numbered regardless of whether they were created in one or more laboratories. Sequential numbers may be obtained from MGD (email to: nomen@informatics.jax.org).
Examples:
CXB Recombinant inbred mouse strain derived from a cross of BALB/c x C57BL/6J.
Multiple RI strains derived from the same strain progenitors are given serial numbers.
Examples:
BXD1, BXD2, BXD3 Members of the BXD set of mouse RI strains derived from a cross of C57BL/6 x DBA/2. HXB1, HXB2, HXB3 Members of the HXB set of rat RI strains derived from a cross of SHR/OlaIpcv x BN-Lx/Cub.
If the second strain abbreviation ends in a number (e.g., CX8 RI strains), a hyphen should be used to separate it from the serial number (e.g., CX8-1).
Recombinant inbred strains may be intercrossed for mapping complex traits. Such F1s are called recombinant inbred intercrosses (RIX) and are symbolized the same as F1s between other inbred strains
Example:
(BXD1/Ty X AXB19/Pgn)F1 An F1 between a female BXD1/Ty and a male AXB19/Pgn.
Incipient inbred stocks or inbred strains that are derived from only two parental strains (one of which could be a gene-targeted ES cell line) can be designated using uppercase abbreviations for the two strains, separated by a semicolon. The strain designation preceding the semicolon should be the host and the strain following the semicolon the donor, specifically for targeted mutations where the donor is the ES cell line. When the two progenitor strains do not have a donor/host relationship, the convention followed is the same as when constructing a F1 hybrid designation; that is, the abbreviation of the strain from which the female originated in the first cross is given before the semicolon. Laboratory codes and serial numbers should be used to distinguish strains produced in different laboratories, or multiple strains from the same laboratory. Because these designations may be used for a mixed stock before it is fully inbred, these stocks should not be assumed to be inbred unless accompanied by an inbreeding generation number (e.g., > F20).
Example:
B6;129-Acvr2tm1Zuk A mixed strain derived from C57BL/6J and a 129 ES cell line carrying a targeted knockout of the Acvr2 gene.
A mutant strain, incipient or inbred, derived from more than two progenitor strains or having genetic contribution from an unknown source is considered a "mixed" inbred and may be designated as STOCK followed by a space (i.e., no hyphen) and the mutation(s) or chromosome anomaly it carries.
Example:
STOCK Rb(16.17)5Bnr An inbred strain of unknown or complex background carrying the Robertsonian translocation Rb(16.17)5Bnr.
Once such a mutant stock achieves inbred status, it should be given the appropriate strain designation. It may be designated using the symbols for the genetic mutations it carries in all uppercase, provided the symbols are short. Because the change in strain name is optional, though strongly recommended, some strains designated as STOCK may be inbred.
Example:
JIGR/Dn An inbred strain developed from a mixed background stock carrying the mutation gr (grizzled) and the ji (jittery) allele of Atcay.
When a mutant allele or chromosomal aberration is maintained by crossing animals bearing the mutation to an F1 hybrid at every generation or at alternate generation(s), the stock is designated by the symbol that would be used for that F1, but without the "F1" suffix, and followed by the appropriate allele or chromosome anomaly symbol.
Examples:
B6C3Fe a/a-Dh The Dh (dominant hemimelia) mutation is maintained by crossing to a (B6C3Fe a/a)F1 at each generation, but the stock itself is not an F1.
Recombinant Congenic (RC) Strains are formed by crossing two inbred strains, followed by a few (usually two) backcrosses of the hybrids to one of the parental strains (the "recipient" strain), with subsequent inbreeding without selection for any specific markers (Demant and Hart, 1986). Such inbred strains will consist of the background recipient strain genome interspersed with homozygous segments of the donor (the amount of donor strain genome depending on the number of original backcrosses, 2 backcrosses will give on average 12.5%).
RC Strains should be regarded as fully inbred when the theoretical coefficient of inbreeding approximates that of a standard inbred strain. For this purpose, one generation of backcrossing will be regarded as being equivalent to two generations of brother x sister mating. Thus, a strain produced by two backcrosses (N3, equivalent to F6) followed by 14 generations of brother x sister mating (F14) would be fully inbred.
RC strains should be designated by an uppercase abbreviation of the two strains, recipient strain listed first, separated by lowercase "c."
Example:
CcS Recombinant congenic strain between BALB/c recipient and STS donor.
Multiple RC strains derived from the same strain progenitors are given serial numbers.
Example:
CcS1, CcS2, CcS3, etc.
If the second strain abbreviation ends in a number (e.g., 129P2), a hyphen should be used to separate it from the serial number.
Advanced intercross lines (AIL) are made by producing an F2 generation between two inbred strains and then intercrossing in each subsequent generation, but avoiding sibling matings (Darvasi and Soller, 1995). The purpose is to increase the possibility of tightly linked genes recombining.
The symbols should contain the Laboratory code of the laboratory that has produced the line, followed by a colon, the two inbred strain abbreviations, separated by a comma, with the generation number included in the symbol following a hyphen. Generations are designated G3, G4, etc. beginning with the first non-sib cross after the F2 generation.
Example:
Pri:B6,D2-G# This is an AIL stock created at Princeton from the inbred strains C57BL/6 x DBA/2. The G number will increase with each generation.
There are several ways in which inbred strains may differ at only a small part of the genome.
Coisogenic strains are inbred strains that differ at only a single locus through mutation occurring in that strain. Strains containing targeted mutations in ES cells that are then crossed to, and maintained, on the same inbred substrain from which the ES cells were derived can be regarded as coisogenic, but the possibility of mutations elsewhere should be considered. Similarly, chemically or radiation induced mutants on an inbred background can be considered coisogenic, although other genomic alterations could be present. A coisogenic strain may accumulate genetic differences over time by genetic drift unless periodically backcrossed to the parental strain.
Coisogenic strains should be designated by the strain symbol (and where appropriate the substrain symbol) followed by a hyphen and the gene symbol of the differential allele, in italics.
Example:
129S7/SvEvBrd-Fyntm1Sor A targeted mutation of the Fyn gene was produced using the AB1 ES cell line derived from 129S7/SvEvBrd. Chimeric animals were mated to 129S7/SvEvBrd and the allele subsequently maintained on this coisogenic strain.
Example:
C57BL/6JEi-tth The tremor with tilted head mutation in the C57BL/6JEi strain.
In some cases, such mutations will be maintained in heterozygous condition. It should be noted that this means that the strain designation does not reflect the breeding system, nor indicate the specific genotype of a given mouse or rat.
Example:
C57BL/6J-Aqp2cph The congenital progressive hydronephrosis mutation in the aquaporin 2 gene arose on the C57BL/6J strain. It is a coisogenic strain, but because homozygotes are generally juvenile lethal, the strain is maintained by breeding heterozygotes Aqp2cph<
