Apc Xenograft-Applicable mouse models

Apc, the mouse ortholog of human APC, encodes the large scaffold that nucleates the beta-catenin destruction complex, using 15 amino acid and 20 amino acid repeats to bind beta-catenin and SAMP repeats to bind AXIN1 and AXIN2, thereby positioning CK1 alpha and GSK3 beta for the priming and processive phosphorylations that create the beta-TrCP degron. Independently, the armadillo repeat region and C-terminal EB1 and DLG binding sites control microtubule plus end dynamics and mitotic spindle fidelity, so truncating alleles produce both Wnt hyperactivation and chromosomal instability. Mutation position matters enormously: the mutation cluster region retains some repeats and yields intermediate signaling, which is why allelic series such as Min, 1638N and 1322T give different tumor multiplicities. Homozygous null is embryonic lethal, mandating floxed exon 14 or 15 designs with tissue-restricted Cre for intestinal, hepatic or mammary work. Match truncation position to the desired Wnt setpoint rather than assuming all Apc alleles are equivalent.

Work with your strain choice to align human tumor models with the immune profile you need.