a splice donor and β‐galactosidase gene is inserted into intron producing a hypomorphic allele [52].
Enhancer traps are specialized transgenes. One utility of these transgenes is in creating cre‐recombinase driver lines. Enhancer traps of this type that are currently being created may include a minimal promoter, introns, a cre‐recombinase cassette (sometimes fused with another element such as ERT2), and polyA sites from different sources. Nomenclature for these enhancer traps consists of 4 parts as follows: Et, prefix for enhancer trap; cre recombinase cassette, portion in parentheses (for example, cre, icre, or cre/ERT2 [if fused with ERT2]); line number or serial number to designate lab trap number or serial number; Lab code: ILAR code identifying the creator of this enhancer trap; Examples include: Et(icre)754Rdav (for Enhancer trap 754, Ron Davis) and Et(cre/ERT2)2047Rdav (for Enhancer trap 2047, Ron Davis) [53].
Transposon‐induced mutations utilize transposases (e.g. sleeping beauty) to mobilize integrated transposon concatemers flanked by long terminal repeats (LTR) to insert into small base pair recognition sequences [54]. When integration of the transposon does not disrupt the LTR, these elements can be remobilized and “hop” into different sites located either on the same chromosome or a different one. Transposons can insert sequences to be expressed as well as disrupting gene expression at integration site. Transposon‐induced alleles are denoted with “Tn,” the transposon concatemer (specifying the transposase), a line number (followed by a period “.” and additional serial number in the case of remobilization), and ILAR‐registered laboratory code. In the transposon‐induced mutation Slc16a10Tn(sb‐lacZ,GFP)1.4Tcb (line 4 containing reintegration of a sleeping beauty‐specific transposon that expressed lacZ and GFP from Dr. Thomas Brodnicki), transposition of the expression cassette into intron 1 produces a null allele [55].
In many cases, a large number of transgenic lines are made from the same gene construct and only differ by tissue specificity of expression. The most common of these are transgenes that use reporter constructs or recombinases (e.g. GFP, lacZ, cre), where the promoter should be specified as the first part of the gene insertion designation, separated by a hyphen from the reporter or recombinase designation. The SV40 large T antigen is another example. The use of promoter designations is helpful in such cases. Examples include Tg(Wnt1‐LacZ)206Amc, in which the mouse has a LacZ transgene with a wingless‐type mouse mammary tumor virus (MMTV) integration site family, member 1 (Wnt1) promoter, from mouse line 206 created in the laboratory of Andrew McMahon [56]. Another example is Tg(Zp3‐cre)3Mrt in which the cre transgene has a zona pellucida glycoprotein 3 (Zp3) promoter, the third transgenic mouse line from the laboratory of Gail Martin [57].
Summary
Mouse genetic nomenclature can be confusing at first, and is often considered to be unimportant by investigators. However, there are many sources of help and support, discussed above, and the effort needed to become fluent in the language of strains and mutants is much less than the potential effort needed to rescue badly planned experiments or recoup the costs involved in using the wrong mice. It is also essential for the replication of experiments, both yours and those whose resources you intend to use, and the sharing of your data. We hope that this commentary lays out clearly why an appreciation and functional knowledge of nomenclature is not only helpful but essential for those using mice as a model system.
Acknowledgments
This work was supported in parts by grants from the National Institutes of Health (R01 CA089713 and HG000330).
References
1 1 McKusick, V.A. (1969). On lumpers and splitters, or the nosology of genetic disease. Perspect Biol. Med. 12 (2): 298–312.
2 2 Simon‐Sanchez, J. and Gasser, T. (2015). Parkinson disease GWAS: the question of lumping or splitting is back again. Neurology 84 (10): 966–967.
3 3 Schofield, P.N., Bubela, T., Weaver, T. et al. (2009). Post‐publication sharing of data and tools. Nature 461 (7261): 171–173.
4 4 Low, B.E., Kutny, P.M., and Wiles, M.V. (2016). Simple, efficient CRISPR‐Cas9‐mediated gene editing in mice: strategies and methods. Methods Mol. Biol. 1438: 19–53.
5 5 Snell, G.D. (1941). Biology of the Laboratory Mouse, 1e. New York, NY: McGraw‐Hill.
6 6 Husler, M.R., Beamer, W.G., Boggess, D. et al. (1998). Neoplastic and hyperplastic lesions in aging C3H/HeJ mice. J. Exp. Anim. Sci. 38 (4): 165–180.
7 7 Sundberg, J.P., King, L.E. Jr., Bosenberg, M. et al. (2020). Animal models of skin disease. In: McKee's Pathology of the Skin with Clinical Correlations. 2, 5e (eds. E. Calonje, T. Brenn, A.H. Lazar and S.D. Billings), 1895–1917. China: Elsevier.
8 8 Li, Q., Berndt, A., Sundberg, B.A. et al. (2016). Mouse genome‐wide association study identifies polymorphisms on chromosomes 4, 11, and 15 for age‐related cardiac fibrosis. Mamm Genome. 27 (5‐6): 179–190. https://doi.org/10.1007/s00335‐016‐9634‐y. Epub 2016 Apr 28.
9 9 Giehl, K.A., Potter, C.S., Wu, B. et al. (2009). Hair interior defect in AKR/J mice. Clin. Exp. Dermatol. 34 (4): 509–517.
10 10 Wu, B., Potter, C.S., Silva, K.A. et al. (2010). Mutations in sterol O‐acyltransferase 1 (Soat1) result in hair interior defects in AKR/J mice. J. Invest. Dermatol. 130 (11): 2666–2668.
11 11 Davisson, M.T., Schmidt, C., Reeves, R.H. et al. (1993). Segmental trisomy as a mouse model for Down syndrome. Prog. Clin. Biol. Res. 384: 117–133.
12 12 Bisaillon, J.J., Radden, L.A. 2nd, Szabo, E.T. et al. (2014). The retarded hair growth (rhg) mutation in mice is an allele of ornithine aminotransferase (Oat). Mol. Genet. Metabol. Rep. 1: 378–390.
13 13 Fox, S. and Eicher, E.M. (1978). The retarded hair growth (rhg) mutation in mice is an allele of ornithine aminotransferase (Oat). Mouse News Lett. 58: 47.
14 14 Griffen, A. (1951). tc – truncate. Mouse News Lett. 5: 31.
15 15 Mulligan, M.K., Mozhui, K., Prins, P., and Williams, R.W. (2017). GeneNetwork: a toolbox for systems genetics. Methods Mol. Biol. 1488: 75–120.
16 16 Li, Q., Philip, V.M., Stearns, T.M. et al. (2019). Quantitative trait locus and integrative genomics revealed candidate modifier genes for ectopic mineralization in mouse models of pseudoxanthoma elasticum. J. Invest. Dermatol. 139 (12): 2447–2457. e7.
17 17 Chesler, E.J., Miller, D.R., Branstetter, L.R. et al. (2008). The Collaborative Cross at Oak Ridge National Laboratory: developing a powerful resource for systems genetics. Mamm. Genome 19 (6): 382–389.
18 18 Philip, V.M., Sokoloff, G., Ackert‐Bicknell, C.L. et al. (2011). Genetic analysis in the Collaborative Cross breeding population. Genome Res. 21 (8): 1223–1238.
19 19 Graham, J.B., Thomas, S., Swarts, J. et al. (2015). Genetic diversity in the collaborative cross model recapitulates human West Nile virus disease outcomes. mBio 6 (3): e00493–e00415.
20 20 Zeiss, C.J., Gatti, D.M., Toro‐Salazar, O. et al. (2019). Doxorubicin‐induced cardiotoxicity in Collaborative Cross (CC) mice recapitulates individual cardiotoxicity in humans. G3 9 (8): 2637–2646.
21 21 Gralinski, L.E., Ferris, M.T., Aylor, D.L. et al. (2015). Genome wide identification of SARS‐CoV susceptibility loci using the Collaborative Cross. PLoS Genet. 11 (10): e1005504.
22 22
