Nomenclature of Genetically Engineered and Mutant Mice
Genetically engineered mice have induced mutations, including transgenes, targeted mutations (knockouts or knockins), and retroviral, proviral or chemically induced mutations.
- Transgenic mice carry a segment of foreign DNA incorporated into their genome via non-homologous recombination (e.g., pronuclear microinjection), infection with a retroviral vector or homologous insertion.
- Targeted mutant mice are produced by first inducing gene disruptions, replacements or duplications into embryonic stem (ES) cells via homologous recombination between the exogenous (targeting) DNA and the endogenous (target) gene. The genetically modified ES cells are then microinjected into host embryos at the eight-cell blastocyst stage. These embryos are transferred to pseudopregnant host females, which then bear chimeric progeny. The chimeric progeny carrying the targeted mutation in their germ line are then bred to establish a line. If the newly established line has a disrupted or deleted gene, it is called a knockout; if it has a new or duplicated gene, it is called a knockin.
- Mice with chemically induced mutations are produced by using a variety of chemicals. One popular chemical mutagen, ethylnitrosourea (ENU), is used to induce point mutations. ENU mutagenesis involves exposing male mice to ENU and then mating the treated males to untreated females. The resultant progeny, many of which carry point mutations, are screened for phenotypes of interest.
Genetically engineered mice are useful for elucidating basic biological processes, studying relationships between gene mutations and disease phenotypes, and modeling human disease. Research applications are included on strain data sheets in the JAX® Mice Database. The applications are compiled using a number of information sources (please refer to Mouse Information Resources), but they are not all-inclusive: rapidly advancing biomedical research continually uncovers new applications and uses for genetically engineered and mutant mice strains.
Some genetically engineered and mutant mice strains have a mutation associated with a specific human disease. If the gene or mutation is orthologous to that in humans and causes the same disease in humans, the strain is designated as a model of the human disease. Manifestation of the genetic mutation (phenotypic expression) may differ between humans and mice. Investigators are strongly encouraged to research recommended mouse models to be sure they are appropriate for their research.
Nomenclature for genetically engineered mice
Nomenclature for chemically induced and targeted mutations follow the same guidelines as described for mice with spontaneous mutations. Gene symbols are italicized. Symbols for recessive genes begin with a lower case letter, and symbols for dominant, semi-dominant, and co-dominant genes begin with an upper case letter, followed by lower case letters. The gene and allele symbols for mutant genes are the same until the gene is cloned.
Alleles are designated either by the chemical mutagen or by the abbreviation “tm” (targeted mutation), followed by a number and the laboratory registration code, and selection criteria superscripted to the gene symbol (e.g., Apoa1tm1Unc).
If a mutation is maintained on a standard inbred background, that inbred strain is the appropriate control. If a mutation is maintained on either a mixed or segregating genetic background, wild-type mice (phenotypically non–mutant mice) from the colony are the best controls. However, because many of our genetically engineered strains are maintained by homozygous matings, wild-type controls from the colony are not available. F2 hybrids are often used as approximate physiological controls for strains carrying targeted mutations (knockouts) maintained on a mixed C57BL/6 x 129 background (designated B6;129). The F2 generation is produced by F1 x F1 matings. The genetic background of C57BL/6J x 129 F2 mice varies among littermates because of gene segregation from the F1 hybrid parents. Although these F2 mice are only an approximate genetic match to the B6;129 background, they do contain only genes derived from either the C57BL/6 or 129 genetic backgrounds. We currently distribute two C57BL/6J x 129 F2 hybrids, differing primarily in their 129 substrain progenitor:
- B6129PF2/J (Stock number 100903)
Parental strains: C57BL/6J-Aw–J and 129P3/J (formerly 129/J).
Suggested control for strains designated B6;129P.
- B6129SF2/J (Stock number 101045)
Parent strains: C57BL/6J and 129S1/SvImJ (formerly 129S3/SvImJ).
Suggested control for strains designated B6;129S.
The controls noted in the strain details for mice carrying targeted mutations are selected to most appropriately match the 129 strain used to derive the ES cell lines (Simpson et al. 1997).
Note: The B6129F1 hybrids are usually less appropriate controls than are the F2 hybrids because the parental alleles of F1 mice are not segregating as opposed to those on a mixed B6;129 background.