Nomenclature of Inbred Mice
Definition and applications
An inbred strain is one that:
- is produced using at least 20 consecutive generations of sister x brother or parent x offspring matings, or;
- is traceable to a single ancestral pair in the 20th or subsequent generation.
All of the standard JAX ® Mice inbred strains have far surpassed 20 generations of inbreeding. Except for the sex difference, mice of an inbred strain are as genetically alike as possible, being homozygous at virtually all of their loci. An inbred strain has a unique set of characteristics that sets it apart from all other inbred strains. Many traits do not vary from generation to generation. Other traits are easily influenced by diet and environmental conditions and therefore may vary from one generation to the next. Some inbred strains carry mutations that may or may not be indicated in the strain designation. For examples, C3H/HeJ mice are homozygous for the retinal degeneration 1 mutation (Pde6b rd1 ) and a defective lipopolysaccharide response allele (Tlr4 Lps–d ), and many inbred strains carry recessive genes affecting coat color. Some of these mutations are cross-referenced in the strain data sheets.
JAX ® Mice inbred strains are particularly well characterized:
- The DNA of 16 JAX ® Mice strains has been sequenced: strain C57BL/6J was sequenced by the publicly funded Mouse Genome Sequencing initiative, and strains 129S1/SvImJ, A/J, AKR/J, BALB/cByJ, BTBR T+ Itpr3 tf /J, C3H/HeJ, CAST/EiJ, DBA/2J, FVB/NJ, MOLF/EiJ, KK/HlJ, NOD/ShiLtJ, NZW/LacJ, PWD/PhJ, and WSB/EiJ were resequenced by the National Institute of Health and Environmental Sciences (NIEHS) Resequencing Project.
- SNP data for the 15 JAX ® Mice strains included in the NIEHS Resequencing Project are publicly available at the NIEHS and Mouse Phenome Database websites; additional SNP data for many JAX ® Mice strains are publicly available at the Mouse SNP Database and the Mouse Phenome Database.
- The majority of the data in the Mouse Phenome Database is for 40 genetically diverse and widely used JAX ® Mice strains.
Substrains are branches of an inbred strain that are either known or suspected to be genetically different from that inbred strain. They form under any of the following three conditions: 1) branches of a strain are separated from the parent colony before the 40th generation of inbreeding; 2) a branch of a strain is maintained separately from the parent colony for more than 20 generations of inbreeding (10 generations in the branch and 10 in the parent colony); and 3) genetic differences from the parent colony are discovered. Unfortunately, the degree of genetic diversity among substrains is often not well characterized.
A limited number of research applications are listed in the strain detail for many of the inbred strains. Investigators are strongly encouraged to research the suitability of a mouse model before ordering. The Mouse Phenome Database, an international effort to collect phenotypic data on commonly used and genetically diverse inbred mouse strains, is a valuable resource. It contains detailed characterizations of a wide array of biochemical and behavioral phenotypes for 40 commonly used and genetically diverse inbred mouse strains; it includes hundreds of measurements for phenotypes relevant to human health, including atherosclerosis, gallstones, alcoholism, hypertension, osteoporosis, airway hyperreactivity, pain responses, blood, neurological, behavioral, and sensory disorders, and toxicity to environmental pollutants; it is continually updated with data generated by contributing scientists.
Helpful hints for understanding inbred strain and gene nomenclature
The parent strain designation of an inbred strain name may consist of capital letters, combinations of letters and numbers, or numbers only (e.g., DBA, C57BL, and 129). Related inbred strains, strains that have a common origin and separated before F20, are given symbols that indicate this relationship (e.g., NZB and NZW; NOD and NON). Substrains are designated by the name of the parent strain followed by a forward slash and a substrain symbol that may be a number and/or the Laboratory Registration Code of the individual or institution that maintains or generated the substrain. For example, DBA/1J, DBA/1LacJ, and DBA/2J are substrains of DBA: the numbers 1 and 2 identify the substrains, Lac is the laboratory code for Laboratory Animal Center at Carshalton, U.K., and J is the laboratory code for The Jackson Laboratory. Because genetic differences in successive substrains accumulate, so do the substrain symbols: A/HeJ is a substrain held first by Heston (He) and now maintained at The Jackson Laboratory (J).
For more detailed information on mouse strain nomenclature, consult the following:
- The Jackson Laboratory: Mouse nomenclature home page
- JAX ® Mice “Nomenclature articles and announcements”
- Interactive tutorial on mouse nomenclature
Revised nomenclature for strain 129 mice
A large degree of genetic diversity among 129 substrains was recently identified by scientists at The Jackson Laboratory (Simpson et al., Nat Genetics 16:19-27, 1997), and subsequently by investigators at Case Western Reserve University (Threadgill et al., Mamm Genome 8:390-393, 1997). Because of the importance of 129 mice in creating “knockout” and other targeted mutant mice, the International Committee on Standardized Genetic Nomenclature for Mice introduced a new nomenclature to distinguish different 129 parental lines and related 129 strains.
The overall result is a nomenclature that specifies groups of strains related by their common parental lineage. The major parental lineages include:
- 129 strains derived from the original parent strain (designated by the letter P)
- 129 strains derived from a congenic strain made by outcrossing to introduce the steel mutation (designated by the letter S)
- 129 strains derived from the 129 congenic that originally carried the teratoma mutation (designated by the letter T).
The numbers following the letters (e.g., P3) distinguish the different 129 parent strains within each lineage.
These nomenclature changes affect the strain names for inbred 129 mice and all mice carrying transgenes, or spontaneous or targeted mutations on a 129 background.
Many targeted mutations (e.g., “knockouts”) are maintained on a mixture of C57BL/6 and a particular 129 strain. This mixed genetic background was previously designated simply B6,129 and subsequently B6;129. Strain names have been revised, e.g., B6;129P or B6;129S, distinguishing between 129 strains of the parental (P) or steel (S) lineages.
The exact origin and breeding history of some spontaneous and targeted mutations maintained on either a 129 background or mixed B6;129 is unknown. Therefore, substrain information has been eliminated from some strain names, and they are designated simply 129 or B6;129.
Two 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 carrying steel and susceptibility to teratomas.
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 minimize 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 Standardized 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,” “Steel,” “Ter” (i.e. susceptible to teratomas) or a genetically contaminated “X” substrain [See JAX® Notes No. 481, Feb. 2001], 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-Lama2 dy will take the strain designation of its partner, i.e. it will be designated 129P1/ReJ-Lama2 dy. This nomenclature change is equivalent to that used to distinguish between RIII and RIIIS, where the latter differs substantially from the former. Table 1 shows the approved new nomenclature for each substrain. Note that 129/Sv (000094), which exists as frozen embryos and has been discovered to be heterozygous at many loci, has not been included on this list as it is clearly not an inbred strain.
129/SvEmsJ (002065) and 129/SvEms (002064) are presumed to be genetically identical. [129S1/SvImJ (002448) was derived from 000090, 129S1/Sv-+p + Tyr-c Kitl Sl-J/+ (formerly Mgf Sl-J/+; see JAX® Notes No. 481, Feb. 2001) in 1995 by selectively breeding out the steel Jackson mutation. Therefore, except for the region surrounding Kitl on Chr 10, these two strains are genetically identical. Designated 129S3/SvImJ in 1999 (Festing et al. 1999), 002448 was renamed in February, 2001 to emphasize its relationship to 129S1/Sv-+p + Tyr-c Kitl Sl-J /+.]
Table 1. New nomenclature for strain 129 mice [modified to incorporate 129S3 to 129S1 change]
Helpful hints for understanding inbred strain nomenclature.