Strains (Nomenclature)

The Animal Resources Centre maintains strains that differ genetically as a consequence of varying breeding programs. These programs are in keeping with internationally recognised procedures as outlined in such references as the “International Index of Laboratory Animals”, 5th edition, by Michael Festing, 1987. The strains to follow represent those presently maintained by the Centre. Information has been provided in a standard format for easy reference. Information on animal characteristics, usage and historical origin has been obtained from “NIH Rodents 1980 Catalogue”, “Inbred Strains in Biomedical Research” by Michael Festing 1979 (see below) and “Origins and characteristics of inbred strains of mice” Michael Festing, Mouse Genome 89(3), 421-548, 1991 and the 3rd issue of each yearly volume thereafter.

Nomenclature

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. A copy of the new guidelines can be viewed at http://www.informatics.jax.org/mgihome/nomen/strains.shtml. Although little has changed as a result of combining the nomenclature rules for the two species, we have continued to publish the previously listed information below in an attempt to better inform researchers interested in either rats or mice and the origins of their names.

Nomenclature Conformance

The rules of nomenclature are continuing to change over time in an attempt to standardise the placement of relevant information into the name of rodents used in research. This standardisation helps to ensure that when a strain is ordered and when work is repeated that the correct strain is used. Although the emphasis has been on the description of transgenic models for the last couple of years, the attention has now turned to the background of the strains used. Since the initial development of inbred rodents in 1906 their use and availability has increased dramatically. With this increase for demand a great diversity of inbred rodent lines have become available to researchers, although the majority of work is still conducted with a handful of strains world wide such as the C57BL/6 mouse. This continual and rapid increase in rodent usage has led to a change in the requirements for identifying physically-isolated mouse colonies for research and paper publication.

Theoretical Example

Two research groups at ARC Institute and MIT Institute are physically isolated, but both maintain colonies of the same inbred line that are used by collaborators in the institutes for research validation. If the two colonies have been recently collected from the same source there should be no problem and the researchers can continue to use the mice with confidence that their research models are genetically identical. Eg: ARC using C57BL/6J MIT using C57BL/6J Over the next couple of years these mice will be subject to a range of natural mutational effects that could lead to genetic divergence. These would include point mutations (expected to occur once every 107-109 nucleotide pairs per generation) that involve the substitution of a single base pair, and frameshift mutations which involve the addition or deletion of base pair(s) leading to a change in the subsequent DNA sequence. Although, with an estimated 95% of the mouse genome containing non-coding DNA the majority of these mutations are expected to occur in non-coding regions or as silent mutations. The ARC Institute maintains its inbred mouse strain as a nucleus colony, with a change-over programme occurring once every 3 months resulting in 10 generations of breeding over a 2.5 year period. With the same taking place at MIT, the two colonies have effectively been separated by 20 generations of breeding. Any papers published from these two institutes should begin to recognise this difference and identify this by recording the filial number in the Materials and Methods sections of their work (eg C57BL/6J F10 @Arc and C57BL/6J F10 @Mit). The “Arc” and “Mit” are Laboratory codes registered with the Institute for Laboratory Animal Research (http://dels.nas.edu/ilar/codes.asp?id=codes). If the research between these two groups continues for a further 2.5 years (totalling 5 years) then both groups have had their individual colonies effectively breeding for 20 generations since their receipt from the common supplier. If a third party were to become interested in the research and wished to duplicate some of the work they could have great difficulty selecting an appropriate model. Without an adequate identification system in place both the ARC and MIT plus the original distributor of the mice will have them listed as C57BL/6J mice. The problem with this is that both the ARC and MIT colonies should now be considered as individual subgroups from the initial colony, not to mention that they now have a combined distance of 40 generations. It is for this reason that the Mouse Genomic Nomenclature Committee (MGNC) proposed to change the requirement for adding a Laboratory Code designation to the end of an isolated colony�s name to 20 generations instead of the previously adopted 100. As a result the mice at the ARC Institute should now be listed as C57BL/6JArc F20. This will identify the mice as a C57BL inbred mouse strain from subgroup 6 that was previously bred at The Jackson Laboratory but has since been maintained at the ARC Institute for 20 generations (F20).

Nomenclature for rat strains

A capital letter or letters in Roman type designates inbred strains eg. BN, PVG. Four letters or fewer are preferred but an exception is made for strains in common use that do not conform eg. F344, DONRYU. Strains from a common origin are regarded as related and are given symbols that bring the strains together in alphabetical lists (eg. WI, WA, WAG, WF). Substrains are shown by a forward slash following the parental strain, then a number eg BN/1, BN/2. The founding strain is designated as /1 but the use is optional. A laboratory code is also used eg. BN/1 Arc. Mutant and congenic strains are designated by the strain symbol, forward slash, substrain symbol and laboratory code followed by a hyphen and the gene symbol eg. LEW/Han-ci. When the mutant or introduced gene exists in the heterozygous state it is indicated by a forward slash after the gene symbol followed by a +, eg. LEW/N – rnu/+. Recombinant inbred strains are indicated by the capital X with no intervening spaces between the strains and the parental strain designations are abbreviated eg. LEW and BN recombinants are designated LXB. RT followed by a number designates alloantigenic (immunogenetic) systems. RT1 is the MHC designation and RT2, RT3 and RT8 are blood group (red cell) antigens. Haplotypes are designated by superscript letters from a to u omitting r, eg. PVG/c-RT7b. Reference: Definition, Nomenclature and Conservation of Rat Strains, Committee on Rat Nomenclature, ILAR News, 34, Number 4, S1-S26, 1992.

Nomenclature for inbred mouse strains

Capital letters, combinations of letters and numbers or numbers only, eg. DBA, C3H, and 129, designate inbred strains. Related inbred strains have a common origin, were separated prior to F20 and are given symbols that indicate this relationship, eg. NZB and NZW; NOD, NON, and NOR. Substrains are designated by the name of the parent strain followed by a slash and a substrain symbol that may be a number or the letter(s) designating the individual or institution maintaining the substrain or both. eg. DBA/1J and DBA/2J are substrains of DBA. The numbers 1 and 2 identify the substrain, and J refers to The Jackson Laboratory. Where successive genetic differences arise in an inbred strain leading to successive substrain formation, the substrain symbols are accumulated, since the genetic differences too will be cumulative; eg. C3H/HeJ  is a substrain held first by Heston and now at The Jackson Laboratory. The symbol @ in a strain means held for >10 generations eg. C57BL/6J@Arc C57BL/6J@Arc. The substrain designation is added after the strain has been maintained as a closed colony for 20 generations. Following the above example when the C57BL/6J strain has been maintained at the Animal Resources Centre for 20 generations (approximately 5 years) it is renamed C57BL/6JArc.

Revised Nomenclature for Strain 129 Mice

Need for revised nomenclature

Two recent papers (Simpson et al., 1997; Threadgill et al., 1997) have shown that there is substantial genetic variation among substrains of this important inbred strain. Some of this has apparently arisen as a result of genetic contamination, and the rest appears to be due to residual heterozygosity and/or “contaminant” alleles introduced during various backcrossing programs such as in the production of congenic strains. Correct identification and designation of substrains is essential if the genotype of the mouse strain is to be matched accurately with an appropriate embryonic stem cell line in the development of “knockout” strains. Unfortunately, current nomenclature makes this difficult. Thus substrains 129/SvJ and 129/SvJae are very different, but this is not immediately obvious even to someone with a good understanding of nomenclature rules. Moreover, some substrains can only be accurately identified using nomenclature involving quite complex gene symbols. Thus, in view of the widespread use of these strains by people with little understanding of genetic nomenclature, it seems sensible to introduce new, simpler, nomenclature which will minimise future misunderstandings particularly as investigators have sometimes referred to different substrains as simply “129”, adding further confusion.

The new nomenclature

The following new nomenclature has been approved by the Committee on Standardised Genetic Nomenclature for Mice.  The aim is to provide short symbols that distinguish different substrains when they are abbreviated from the frequently long and  complicated substrain symbols, either in common usage or in manuscripts. The new nomenclature is based on the substrains identified  and defined in terms of microsatellite markers by Simpson et al., (1997). A letter and a number have been introduced in front of the slash  that will unequivocally identify each of the substrains. The letter is either P, S, T or X indicating whether it is a “Parental”, “Ter”  (ie. susceptible to teratomas) or a genetically contaminated “X” substrain, respectively. A number will be used to differentiate between  substrains within each grouping, working from left to right in Fig. 2 of Simpson et al., (1997). All existing substrain symbols and  gene symbols will be retained. The only change is the introduction of a letter and a number in front of the slash. A genuine congenic strain  such as 129/ReJ-Lama2dy will take the strain designation of its partner, ie. it will be designated 129P1/ReJ-Lama2dy. This nomenclature change is equivalent to that used to distinguish between RIII and RIIIS, where the latter differs substantially from the former.  

The names of recombinant inbred strains consist of the strain names of the parental lines separated by a capital X.  The strain names are also shortened as follows:Nomenclature for recombinant inbred strains

StrainAbbreviation
AKRAK
BALB/cC
C3HC3
C57BL/6B6
C57BL/10B10
C57BRBR
DBA/1D1
DBA/2D2
As an example CXB refers to BALB/cXC57BL. Different parallel strains of the same series are designated by a number after the parental strain eg CXB5, CXB2, CXB19 etc. An exception occurs where the strain was already named before the rules of nomenclature were established. Such is the case with the CXBD-CXBK series.

Nomenclature for congenic strains

Congenic strains produced by repeated crosses on to an inbred strain are designated by the full or abbreviated (above) strain name of the background strain followed by a full stop (.) then the abbreviated name of the donor strain, followed by a hyphen and the gene symbol. If several strains are developed from the same donor strain they are distinguished by a number and/or letter in parenthesis. Eg
B10. A (2R)- H-2h2
1 2 3 4
  1. B10 = C57BL/10ScSn
  2. A = A/J strain
  3. (2R) = subline
  4. H-2h2 = gene symbol

Nomenclature for spontaneous mutant strains

Spontaneous mutant stocks or strains are mice carrying one or more mutated genes in homozygous or in heterozygous conditions. Gene symbols in strain names are brief and intended to convey essential information concerning the genotype of the strains or stocks. The symbols usually represent an abbreviation of the gene name and the way in which the strain or stock is maintained in a colony. The 1994 International Committee on Standardised Genetic Nomenclature for Mice voted to change the symbols for mutations. Where the gene responsible for the mutation is known and has been cloned, the gene symbol is given with the old gene symbol superscripted. All spontaneous mutation symbols follow a hyphen after the background strain and are written in italics. A lower case (recessive) or upper case (dominant) first letter of the old gene symbol denotes the mode of inheritance. The first letter of gene symbol is upper case followed by lower case letters or numbers. The following are examples:
ExampleDescription
B6.Cg-ax or B6C3Fe-a/a-Csf1opWhen the strain is maintained by continued backcrossing to an inbred strain or F1 hybrid, the symbol(s) for the introduced gene(s) is given once. Non mutant controls are available from the same strain. Note: Strains maintained by backcrossing to F1 hybrids are not true F1′s and are segregating at all genes for which the F1 parental strains differ.
CBA/CaH-kdWhen a mutation is maintained on an inbred strain background by mating homozygous mutants together, the introduced gene symbol is given once. Non mutant controls from a related strain must be used.
BALB/cBy-cla/+When a mutation is maintained on an inbred strain background by brother x sister matings with forced heterozygosis, the gene symbol is followed by the designation: /+. Non mutant controls are available from the same strain.
During 1994, the “International Committee on Standardised Genetic Nomenclature for Mice” voted to change the symbols of mutations that  have been cloned to show they are mutant alleles of the cloned genes. The mutation’s symbol is changed by superscripting the mutation symbol  to the cloned gene symbol. For example, the nu (nude) mutation in the Foxn1 (human forkhead box N1) gene became Foxn1nu.  If the original mutation symbol already has a superscript, the mutation and allele superscript symbols are placed on one line in the new  superscript and hyphenated eg. the Mobr(Mottled- Brindle) mutation becomes Atp7aMo-br.  When a mutation is shown to occur in a cloned candidate gene, the first letter of the gene symbol may remain upper case and the  inheritance pattern may be conveyed in the allele symbol, eg. the scid (recessive severe combined immune deficiency)  gene allele at the Prkdc locus gene become Prkdcscid. For a complete listing of nomenclature rules see  http://www.informatics.jax.org/mgihome/nomen/. Some strains are maintained by using coat colour markers. An example of this is diabetes. Leprdb is maintained in  repulsion with a closely linked marker misty, m, a coat colour gene. The mating system used, m +/+ Leprdb x m +/+  Leprdb, produces three genotypes all of which are phenotypically distinguishable. The + Leprdb/+ Leprdb mice are fat and black, the m +/+ Leprdb mice are lean and black, and the m +/m + mice are lean and misty (dark grey).

Nomenclature for Transgenic Strains

A transgene symbol consist of three parts as follows:

TgX (YYYYYY)#####Zzz

Tg:Transgenic
X:The mode of insertion (Now excluded)
(AAA-BBB):AAA = Promoter, BBB = Transcribed sequences (“-” now excluded)
#####:Laboratory-assigned number
Zzz:Laboratory code.

Mode of Transgenesis

  • X is a letter designating the mode of insertion of the DNA;
  • N for non-homologous insertion,
  • R for insertion via infection with a retroviral vector,
  • H for homologous recombination.

Insert designation:

The second part of the symbol indicates the salient features of the transgene as determined by the investigator. It is in parentheses and consists of no more than eight characters. The insert designation should identify the inserted sequence and indicate important features.

Laboratory-assigned number:

This is a unique number that is assigned by the laboratory to each stably transmitted insertion when germline transmission is confirmed.

Laboratory code:

This is uniquely assigned to each laboratory that produces transgenic animals. It can be the same as the Laboratory Code assigned to producers of genetically defined rodents.

Examples.

C57BL/6J-TgN(CD8Ge)23Jwg. The non-homologous insertion of human CD8 genomic clone Ge into C75BL/6 mice from the Jackson Laboratory (J); the 23rd mouse screened in a series of microinjections in the laboratory of Jon W Gordon (Jwg). 129/J-TgH(SV40Tk)65Rpw. An SV40-thymidine kinase (Tk) transgene targeted by homologous recombination to a specific but anonymous locus using embryonic stem cells derived from mouse strain 129/J. This was the 65th mouse of this series produced in the laboratory of Richard P Woychik (Rpw). Reference: Standardised nomenclature for transgenic animals. Committee on Transgenic Nomenclature, ILAR News 34,(4):45-52, 1992.

Nomenclature for Targetted Mutant Strains

Most targeted mutations (gene knockout or deletion strains) mice are created by the injection of an embryo stem cell (usually 129 strain cell line) into the blastocyst of another inbred strain. This results in a chimeric offspring. The nomenclature is characterised as follows:

X;Y – ###tm**Zzz

Xrecipient strain (abbreviation)
Yembryo stem cell donor strain (abbreviation)
### gene symbol (in italics)
**number of the targeted mutant line (in italics and superscripted)
Zzz laboratory code (in italics and superscripted)
For example:

B6;129 – Apoetm1Unc

This is the first targeted mutation of the Apoe gene made at the University of North Carolina and maintained on an inbred or incipient inbred strain whose genetic background is derived from C57BL/6 and 129 strains. If this strain was backcrossed >6 times onto the C57BL/6 background then the semicolon (;) would be dropped and replaced with a period (.). Note: the comma in the mixed strain designation (B6,129) has been replaced with a semicolon (B6;129) to more clearly distinguish transgenes or mutations maintained on a mixed genetic background from congenic strains.