Dp(7Sult1a1‐Spn)7Yah: Duplication in Chromosome 7 from the gene Sult1a1 to the gene Spn that was the seventh duplication made by Dr. Yann Herault (http://www.informatics.jax.org/accession/MGI:6342919).
In(5)2Rk: Inversion in Chromosome 5 that was the 5th inversion generated by Dr. Thomas Roderick (http://www.informatics.jax.org/accession/MGI:3789592).
Rb(11.16)2H: Robertsonian translocation between Chromosomes 11 and 16 that was the second Robertsonian translocation generated at Harwell (http://www.informatics.jax.org/accession/MGI:104106).
T(12;16)1Cje: Reciprocal translocation between Chromosomes 12 and 16 that was the first reciprocal translocation generated by Dr. Charles Epstein (http://www.informatics.jax.org/accession/MGI:1860491).
While chromosomal aberrations were traditionally generated primarily through radiation experiments, modern genetic engineering techniques permit more engineered strategies [43]. Transgenic insertions are also a form of chromosomal aberration, and they are covered in the “Genetically Engineered Mice” section.
Genetically Engineered Mice
There are three basic types of genetically engineered mice: transgenic, targeted, and endonuclease‐mediated. Different nomenclature is used to distinguish these.
Transgenic mice can be created to overexpress a gene, express a gene not normally found in mice (green fluorescent protein [GFP] from jellyfish), conditionally express genes, and many other engineered approaches not found normally in nature.
Transgenic nomenclature can be complex, especially as some transgenes still use older formats (Table 3.13). All transgenes begin with Tg followed by information in parentheses then a founder line number and lab code. If a single gene driven by its own promoter is inserted, then the information in the parentheses is simply that gene symbol, not italicized. The information in the parentheses begins with the promoter, a hyphen, then information about the expressed sequence(s). For example, C57BL/6J‐Tg(Mt1‐Tnfsf4)1Pgn/Pgn has a transgenic insertion of mouse tumor necrosis factor (ligand) superfamily, member 4 (Tnfsf4) gene under the control of the metallothionine promoter coisogenic on the C57BL/6J background and is the first transgenic line with these components made by Dr. Beverly Paigen [44].
Table 3.13 Nomenclature for transgenic mice.
| FVB/NJ‐Tg(KRT14‐HPV18E7)CSun/SunFVB/NJ = genetic background of the strainTg = Transgene insertionKRT14 = Human KRT14 promoterHPV18E7 = Human papillomavirus 18 E7 geneC = transgenic lineSun = strain lab code, John P. Sundberg |
| B6N.Cg‐Tg(KRT14‐cre)1Amc/JB6N = Congenic host strain carrying the allele, C57BL/6NCg = donor strain is not known (C57BL/6 x CBA)F1Tg = Transgene insertionKRT14 = Human keratin 14 genecre = cre‐recombinase expressing1Amc = line 1, Andrew P. McMahonJ = strain lab code, The Jackson Laboratory |
Targeted, Endonuclease‐Mediated, Enhancer or Gene Trap, Transposon‐Induced, and Transgenic Mutations
Targeted mutations were initially generated to produce mutant mice with inactivation of one specific gene, the so‐called “knockout” mouse lines. Targeted mutations can also have a foreign gene or gene segment inserted into a target gene, resulting in expression of the foreign gene under control of the endogenous promoter. These are termed “knock‐in” mutations. In these cases, the inserted gene symbol is included in parentheses as part of the targeted allele symbol. However, reporter symbols, such as GFP, are not included in allele symbols. Details describing the specifics of knock‐in constructs should be provided in databases or publications, and not in the nomenclature.
In the targeted knock‐in mutation En1tm1(Otx2)Wrst, the coding region of the engrailed 1 gene (En1) was replaced by the orthodenticle homeobox 2 (Otx2) gene, originating from the W. Wurst laboratory [45]. For the Cd19 antigen targeted knock‐in mutation Cd19tm1(cre)Cgn, cre‐recombinase was inserted in‐frame in exon 1 [46]. The allele expresses cre‐recombinase specifically in B‐lineage cells throughout development. The apolipoprotein E targeted knock‐in mutation (Apoetm1(APOE*2)Mae) has a DNA fragment containing exons 2–4 of a human APOE2 isoform replacing the equivalent portion of the mouse Apoe gene. The human protein is expressed from this allele and the endogenous mouse protein is undetectable.
When a targeting vector is used to generate multiple germline‐transmissible alleles, such as in the cre‐Lox system, the original knock‐in of loxP would follow the regular tm designation rules. If a second heritable allele was then generated after mating with a cre‐recombinase transgenic mouse, it would retain the parental designation followed by a decimal point and serial number. For example, Tfamtm1Lrsn designates a targeted mutation where loxP was inserted into the transcription factor A, mitochondrial (Tfam) gene [47]. Tfamtm1.1Lrsn (note: tm1Lrsn vs. tm1.1Lrsn) designates the derivative germline transmissible allele generated after mating with a cre‐recombinase transgenic mouse. Note that somatic events generated in offspring from a Tfamtm1Lrsn bearing mouse and a cre‐recombinase transgenic that cause disruption of Tfam in selective tissues would not be part of strain nomenclature.
Mutagenesis using targeted endonuclease‐cleavage technologies (CRISPR, Zinc Finger endonuclease, or TALEN) create site‐targeted genomic changes by either non‐homologous end joining resulting in random indels (insertion/deletions), or homologous recombination with a donor plasmid to generate specific sequence alterations (floxed, point mutations, insertion of exogenous sequence, etc.). While there is no standard for naming endonuclease‐mediated mutations across species, mouse, rat, and Xenopus designate such mutation with “em” [48] followed with the serial number of endonuclease‐mediated mutation for the generating laboratory, and the ILAR‐registered laboratory code (e.g. Abcb1aem1Sbkv for endonuclease‐mediated mutation 1 from the laboratory of Dr. Sergei B Koralov in adenosine triphosphate (ATP)‐binding cassette, sub‐family B [MDR/TAP], member 1A gene) [49]. Endonuclease‐mediated mutation nomenclature mirrors targeted allele nomenclature in regard to inserted expressed sequences (http://www.informatics.jax.org/mgihome/nomen/gene.shtml#endim). When endonuclease‐mediated mutations are used to produce multigenic mutations either through direct targeting or recombination between previously targeted sites, chromosomal aberration nomenclature is used in the absence of a marker designating the region affected (to be added to the nomen webpage). For example, Del(5Kit‐Nmu)2Staka (deletion, Chr 5, Satoru Takahashi 2) describes the 1.07 Mb deletion produced by CRISPR/Cas targeting of a region 240 kb upstream of Kit and 81 kb downstream of Nmu [50].
Gene trap alleles are produced by random integration of constructs containing splice acceptors and other sequences that prematurely terminated transcription disrupting gene expression [51]. Alleles generated by the integration of a gene trap are represented with “Gt,” the mutant cell line in parenthesis, and ILAR‐registered laboratory code. For example, in Dnajb9Gt(KST256)Byg
