On 2014 Apr 28, Jim Woodgett commented:

SB415286 inhibits both the GSK-3alpha and GSK-3beta isoforms (encoded by different genes) with similar potency. Beta-catenin is only stabilized when Axin-associated GSK-3 (a mixture of both alpha and beta isoforms) is disrupted following Wnt receptor binding - causing association with of Axin with LRP5/6 (PMID 22682247). Knocking out GSK-3 alpha or GSK-3beta typically has no measurable effect on beta-catenin levels as only 5-10% of cellular GSK-3 is bound to Axin and each isoform fully compensates for the other in this pathway (e.g. PMID 17543867). Hence, the observed effects are likely (in the case of the drug) not GSK-3beta specific and in the case of the KO, likely reflect increased sensitivity of the residual GSK-3alpha to an endogenous signal (presumably Wnt).

On 2014 Apr 28, Jim Woodgett commented:

SB415286 inhibits both the GSK-3alpha and GSK-3beta isoforms (encoded by different genes) with similar potency. Beta-catenin is only stabilized when Axin-associated GSK-3 (a mixture of both alpha and beta isoforms) is disrupted following Wnt receptor binding - causing association with of Axin with LRP5/6 (PMID 22682247). Knocking out GSK-3 alpha or GSK-3beta typically has no measurable effect on beta-catenin levels as only 5-10% of cellular GSK-3 is bound to Axin and each isoform fully compensates for the other in this pathway (e.g. PMID 17543867). Hence, the observed effects are likely (in the case of the drug) not GSK-3beta specific and in the case of the KO, likely reflect increased sensitivity of the residual GSK-3alpha to an endogenous signal (presumably Wnt).