There are various “reporter transgenes” that respond to Wnt signals in intact animals and therefore, as far as one can know, reflect endogenous Wnt signaling (reviewed in Barolo, 2006). These reporters are based on a multimerized TCF binding site, driving expression of LacZ or GFP. Other lines allow for lineage tracing of Wnt responding cells, using the Cre/ERT2 gene inserted into Wnt target genes.
Animal strain (linked to resource)
|TOP-GAL (obtain from Jackson Labs)||3 TCF sites, c-fos promoter, LacZ||Gupta and Fuchs (1999)|
|BAT-GAL||TCF sites, Siamois promoter||Maretto et al (2003),|
|ins-TOPEGFP, ins-TOPGAL||TCF sites, LacZ or GFP, insulator elements||Moriyama (2007) (mice not available anymore)|
|LEF-EGFP||TCF sites, EGFP||Currier et al, (2010).|
|TCF/Lef:H2B-GFP reporter (obtain from Jackson labs)||TCF sites, H2B-GFP,||(Ferrer-Vaquer et al 2010)|
|Axin2-LacZ (obtain from Jackson Labs)||Insert of LacZ into Axin2, Wnt target gene||Lustig et al, (2002)|
|Axin2-d2EGFP||Axin2 promoter, EGFP||Jho et al, (2002),|
|Axin2-rtTA (obtain from Jackson Labs)||Axin2 promoter, rtTA||Maruyuma, 2010|
|Axin2-mTurquoise2||Insert of mTurquoise into Axin2, Wnt target gene||de Roo, 2017|
|Lgr5tm1(cre/ERT2) (obtain from Jackson Labs)||Cre/ERT2 insert into LGR5, Wnt target gene||Barker et al (2007)|
|Axin2-Cre/ERT2 (obtain from Jackson Labs)||Cre/ERT2 insert into Axin2, Wnt target gene||Van Amerongen (2012)|
|Tcf3-CreER||Cre/ERT2 into TCF3||Howard et al, (2014)|
|TOPdGFP Zebrafish||TCF sites, dGFP||Dorsky and Moon (2002)|
|Tcf/Lef-miniP:dGFP Zebrafish||TCF sites, dGFP||Shimizu et al, 2012|
|Axin2P2A-rtTA3-T2A-3xNLS-SGFP2||multi-cistronic targeting cassette at the 3’ end of Axin2||van de Moosdijk et al, 2020|
|Axin2-mGFP||Insert of mGFP into Axin2, Wnt target gene||Wang et al, 2021|
In response to the often-asked question “what is the best Wnt reporter”, there is no simple answer. In our experience, Axin2/Conductin is widely expressed in areas where one would expect it, and might be an optimal reporter for many tissues. However, there are cells (in the lung for example) that are positive for the TOP-GAL reporter and negative for Axin2-based reporters (Al Alam et al, 2011). The problem of reliably detecting Wnt signaling in vivo is compounded by difficulties in assessing Wnt gene expression itself (which is best done by in situ hybridization as antibodies are rarely good enough), or in finding other independent hallmarks of Wnt signaling (see Barolo, 2006 and Al Alam et al, 2011).
It should be noted that there are variations in Axin2 linked phenotypes, ranging from homozygous Axin2-LacZ animals being viable and fertile with relatively minor phenotypes (Lustig et al, (2002), to homozygous Axin2-mGFP lethality (Wang et al, 2021). In these strains, the LacZ and mGFP reporter genes were inserted in the same location in Axin2.
In addition, homozygous Axin2-CreERT2 mice in The Jackson Laboratory colony are born at a significantly reduced frequency (~5% in heterozygous crosses). Due to the disruption of the targeted gene, animals may display minor phenotypes similar to Axin-lacZ mutant targeted to the same genetic location. Homozygotes may display malformations of skull structures. See van de Moosdijk et al, 2020 for a detailed analysis of Axin2 associated phenotypes.