R26Fucci2aR

The R26Fucci2aR and R26Fucci2a cell cycle reporter mice were generated by knocking a Cre inducible version of the Fucci2a biosensor into the ROSA26 locus in mouse embryonic stem cells by homologous recombination (Mort et al 2014). They are available from the RIKEN and from EMMA repositories – for further details please see our resources page. They allow ubiquitous or Cre activated expression of the Fucci2a cell cycle biosensor:

Activation of the R26Fucci2aR allele by Cre-recombinase
Activation of the R26Fucci2aR allele by Cre-recombinase

Below are images of lung development from R26Fucci2a ubiquitous reporter mice:

Fucci2a expressing mouse lung in culture.

In this following movie we track branching morphogenesis in E11.5 cultured mouse lungs from Sox17-Cre;R26Fucci2aR mice (Engert et al 2009).

Sox17-2A-iCre: a knock-in mouse line expressing Cre recombinase in endoderm and vascular endothelial cells. Engert S, Liao WP, Burtscher I, Lickert H. Genesis. 2009 Sep;47(9):603-10. doi: 10.1002/dvg.20540.

Fucci2a: a bicistronic cell cycle reporter that allows Cre mediated tissue specific expression in mice. Mort RL, Ford MJ, Sakaue-Sawano A, Lindstrom NO, Casadio A, Douglas AT, Keighren MA, Hohenstein P, Miyawaki A, Jackson IJ. Cell Cycle. 2014;13(17):2681-96. doi: 10.4161/15384101.2015.945381.

It has been wonderful to see the many diverse experimental questions our cell cycle biosensor expressing mouse lines (R26Fucci2aR and R26Fucci2a) have been applied to.

Here is a non exhaustive list of publications from other groups that have used our technology so far:

Pyramidal cell regulation of interneuron survival sculpts cortical networks. Wong FK, Bercsenyi K, Sreenivasan V, Portalés A, Fernández-Otero M, Marín O. Nature. 2018 May;557(7707):668-673. doi: 10.1038/s41586-018-0139-6. Epub 2018 May 30. PMID: 29849154 Free PMC article.
Oligodendrocyte Progenitor Cells Become Regionally Diverse and Heterogeneous with Age. Spitzer SO, Sitnikov S, Kamen Y, Evans KA, Kronenberg-Versteeg D, Dietmann S, de Faria O Jr, Agathou S, Káradóttir RT. Neuron. 2019 Feb 6;101(3):459-471.e5. doi: 10.1016/j.neuron.2018.12.020. Epub 2019 Jan 14. PMID: 30654924 Free PMC article.
Endocycle-related tubular cell hypertrophy and progenitor proliferation recover renal function after acute kidney injury. Lazzeri E, Angelotti ML, Peired A, Conte C, Marschner JA, Maggi L, Mazzinghi B, Lombardi D, Melica ME, Nardi S, Ronconi E, Sisti A, Antonelli G, Becherucci F, De Chiara L, Guevara RR, Burger A, Schaefer B, Annunziato F, Anders HJ, Lasagni L, Romagnani P. Nat Commun. 2018 Apr 9;9(1):1344. doi: 10.1038/s41467-018-03753-4. PMID: 29632300 Free PMC article.
Fibroblast state switching orchestrates dermal maturation and wound healing. Rognoni E, Pisco AO, Hiratsuka T, Sipilä KH, Belmonte JM, Mobasseri SA, Philippeos C, Dilão R, Watt FM. Mol Syst Biol. 2018 Aug 29;14(8):e8174. doi: 10.15252/msb.20178174. PMID: 30158243 Free PMC article.
A stochastic framework of neurogenesis underlies the assembly of neocortical cytoarchitecture. Llorca A, Ciceri G, Beattie R, Wong FK, Diana G, Serafeimidou-Pouliou E, Fernández-Otero M, Streicher C, Arnold SJ, Meyer M, Hippenmeyer S, Maravall M, Marin O. Elife. 2019 Nov 18;8:e51381. doi: 10.7554/eLife.51381. PMID: 31736464 Free PMC article.
Defining the Identity and Dynamics of Adult Gastric Isthmus Stem Cells. Han S, Fink J, Jörg DJ, Lee E, Yum MK, Chatzeli L, Merker SR, Josserand M, Trendafilova T, Andersson-Rolf A, Dabrowska C, Kim H, Naumann R, Lee JH, Sasaki N, Mort RL, Basak O, Clevers H, Stange DE, Philpott A, Kim JK, Simons BD, Koo BK. Cell Stem Cell. 2019 Sep 5;25(3):342-356.e7. doi: 10.1016/j.stem.2019.07.008. Epub 2019 Aug 15. PMID: 31422913 Free PMC article.
Epigenetic remodelling licences adult cholangiocytes for organoid formation and liver regeneration. Aloia L, McKie MA, Vernaz G, Cordero-Espinoza L, Aleksieva N, van den Ameele J, Antonica F, Font-Cunill B, Raven A, Aiese Cigliano R, Belenguer G, Mort RL, Brand AH, Zernicka-Goetz M, Forbes SJ, Miska EA, Huch M. Nat Cell Biol. 2019 Nov;21(11):1321-1333. doi: 10.1038/s41556-019-0402-6. Epub 2019 Nov 4. PMID: 31685987 Free PMC article.
Single-Cell Analysis Reveals a Hair Follicle Dermal Niche Molecular Differentiation Trajectory that Begins Prior to Morphogenesis. Gupta K, Levinsohn J, Linderman G, Chen D, Sun TY, Dong D, Taketo MM, Bosenberg M, Kluger Y, Choate K, Myung P. Dev Cell. 2019 Jan 7;48(1):17-31.e6. doi: 10.1016/j.devcel.2018.11.032. Epub 2018 Dec 27. PMID: 30595533 Free PMC article.
Mutant EZH2 Induces a Pre-malignant Lymphoma Niche by Reprogramming the Immune Response. Béguelin W, Teater M, Meydan C, Hoehn KB, Phillip JM, Soshnev AA, Venturutti L, Rivas MA, Calvo-Fernández MT, Gutierrez J, Camarillo JM, Takata K, Tarte K, Kelleher NL, Steidl C, Mason CE, Elemento O, Allis CD, Kleinstein SH, Melnick AM. Cancer Cell. 2020 May 11;37(5):655-673.e11. doi: 10.1016/j.ccell.2020.04.004. PMID: 32396861 Free PMC article.
Lgr5+ intestinal stem cells reside in an unlicensed G1 phase. Carroll TD, Newton IP, Chen Y, Blow JJ, Näthke I. J Cell Biol. 2018 May 7;217(5):1667-1685. doi: 10.1083/jcb.201708023. Epub 2018 Mar 29. PMID: 29599208 Free PMC article.
Composite regulation of ERK activity dynamics underlying tumour-specific traits in the intestine. Muta Y, Fujita Y, Sumiyama K, Sakurai A, Taketo MM, Chiba T, Seno H, Aoki K, Matsuda M, Imajo M. Nat Commun. 2018 Jun 5;9(1):2174. doi: 10.1038/s41467-018-04527-8. PMID: 29872037 Free PMC article.
Hair follicle dermal condensation forms via Fgf20 primed cell cycle exit, cell motility, and aggregation. Biggs LC, Mäkelä OJ, Myllymäki SM, Das Roy R, Närhi K, Pispa J, Mustonen T, Mikkola ML. Elife. 2018 Jul 31;7:e36468. doi: 10.7554/eLife.36468. PMID: 30063206 Free PMC article.