Beyond knockouts: cre resources for conditional mutagenesis
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With the effort of the International Phenotyping Consortium to produce thousands of strains with conditional potential gathering steam, there is growing recognition that it must be supported by a rich toolbox of cre driver strains. The approaches to build cre strains have evolved in both sophistication and reliability, replacing first-generation strains with tools that can target individual cell populations with incredible precision and specificity. The modest set of cre drivers generated by individual labs over the past 15+ years is now growing rapidly, thanks to a number of large-scale projects to produce new cre strains for the community. The power of this growing resource, however, depends upon the proper deep characterization of strain function, as even the best designed strain can display a variety of undesirable features that must be considered in experimental design. This must be coupled with the parallel development of informatics tools to provide functional data to the user and facilitated access to the strains through public repositories. We discuss the current progress on all of these fronts and the challenges that remain to ensure the scientific community can capitalize on the tremendous number of mouse resources at their disposal.
The authors thank Laura Kus, Hongkui Zeng, Marie-Christine Burling, and Lauryl Nutter for information about individual cre driver programs. Special thanks to Caleb Heffner for his help with details and references for the JAX cre characterization program. This work was supported by NIH Grants HG000330 (JTE), HD062499 (JTE), RR032656 (JTE and SAM), DE020052 (SAM), RR026117 (SAM), and EU Grant HEALTH-F4-2009-223487 (JTE, DS, and NR).
- Blake JA, Bult CJ, Kadin JA, Richardson JE, Eppig JT (2011) The Mouse Genome Database (MGD): premier model organism resource for mammalian genomics and genetics. Nucleic Acids Res 39(Database issue):D842–D848Google Scholar
- Eppig JT, Blake JA, Bult CJ, Kadin JA, Richardson JE (2012) The Mouse Genome Database (MGD): comprehensive resource for genetics and genomics of the laboratory mouse. Nucleic Acids Res 40(Database issue):D881–D886Google Scholar
- Forni PE, Scuoppo C, Imayoshi I, Taulli R, Dastru W, Sala V, Betz UA, Muzzi P, Martinuzzi D, Vercelli AE et al (2006) High levels of Cre expression in neuronal progenitors cause defects in brain development leading to microencephaly and hydrocephaly. J Neurosci 26(37):9593–9602PubMedCrossRefGoogle Scholar
- Indra AK, Warot X, Brocard J, Bornert JM, Xiao JH, Chambon P, Metzger D (1999) Temporally-controlled site-specific mutagenesis in the basal layer of the epidermis: comparison of the recombinase activity of the tamoxifen-inducible Cre-ER(T) and Cre-ER(T2) recombinases. Nucleic Acids Res 27(22):4324–4327PubMedCrossRefGoogle Scholar
- Zambrowicz BP, Imamoto A, Fiering S, Herzenberg LA, Kerr WG, Soriano P (1997) Disruption of overlapping transcripts in the ROSA beta geo 26 gene trap strain leads to widespread expression of beta-galactosidase in mouse embryos and hematopoietic cells. Proc Natl Acad Sci USA 94(8):3789–3794PubMedCrossRefGoogle Scholar