Erbb3 Conditional Knockout mouse models

Erbb3, the mouse ortholog of human ERBB3, encodes a pseudokinase family member that binds neuregulin 1 and neuregulin 2 through extracellular domains I and III but carries substitutions in the catalytic loop that render it essentially kinase dead, so it functions as an allosteric activator of a partner kinase and, critically, as the ERBB family member with six YXXM motifs in its C-terminal tail that directly recruit the p85 subunit of PI3K. This makes ERBB3 the dominant conduit to AKT for ERBB2 amplified tumors and the principal mechanism of adaptive resistance to EGFR and ERBB2 targeted agents, since relief of feedback rapidly upregulates ERBB3. Null embryos die at midgestation with cardiac cushion and Schwann cell precursor defects, so conditional alleles are needed for adult work. Humanized ectodomain knockins support testing of ERBB3 antibodies and bispecifics whose epitopes do not cross-react. Choose conditional nulls for PI3K dependency and resistance studies, paired with an epithelial or Schwann cell Cre.

Conditional deletion of Erbb3 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 Erbb3 floxed stock yields usable cohorts.