Gsk3b Conditional Knockout mouse models

Encoding a constitutively active serine and threonine kinase that prefers substrates pre-phosphorylated four residues carboxy-terminal to its site, Gsk3b is the mouse ortholog of human GSK3B and is inhibited by Akt phosphorylation of Ser9 as well as by Wnt-driven sequestration; within the Axin and Apc destruction complex it phosphorylates beta-catenin at Ser33, Ser37, and Thr41 to license betaTrCP-mediated degradation, and it also targets tau, Snai1, Mcl1, Nfatc, and glycogen synthase. Homozygous nulls die at mid-gestation with hepatocyte apoptosis reflecting defective NF-kB survival signaling, so conditional deletion is standard, while a Ser9-to-alanine knockin creates an Akt-resistant kinase that tests whether inhibitory phosphorylation is required in vivo and a kinase-dead allele distinguishes scaffolding from catalysis. Critically, Gsk3a is a genuine paralog with overlapping substrate specificity, and many phenotypes emerge only in double conditional animals, so plan the compound cross and driver together with the primary flox.

Conditional deletion of Gsk3b limits the genetic change to the lineage you choose. That helps in oncology, immunology, and metabolic work where systemic loss would muddy the read. After you confirm Cre specificity, crossing to Gsk3b floxed stock yields usable cohorts.