• HER3, a TAA target, is a member of the epidermal growth factor receptor family and is involved in the regulation of tumor cell growth and differentiation mechanisms. It has been reported that ERBB3 can form heterodimers with other members of the EGFR receptor family, ERBB1 (also known as EGFR, HER1), ERBB2/HER2 and ERBB4/HER4, and activate downstream pathways (PI-3K /Akt, MEK/MAPK, Jak/Stat, etc.). It is involved in the proliferation, differentiation, migration, adhesion, anti-apoptosis and cell transformation of many tumor cells. HER3 is overexpressed in solid tumors such as breast cancer and non-small cell lung cancer, and its downstream signaling pathway is blocked by targeting HER3 antibodies to achieve tumor inhibition, so it becomes an important target for tumor therapy. This target focuses on the development of monoclonal antibodies or drugs coupled with bispecial antibodies or antibodies to members of the same family.

mRNA expression analysis:

• Mouse Her3 mRNA was only detectable in liver of wild-type mice. Human HER3 mRNA was exclusively detectable in liver of homozygous B-NDG hHER3 mice but not in wild-type mice.

Gene targeting strategy for B-NDG hHER3 mice. The exons 1-17 of mouse Her3 gene that encode extracellular domain and transmembrane domain is replaced by human counterparts in B-NDG hHER3 mice. The genomic region of mouse Her3 gene that encodes signal peptide and cytoplasmic portion is retained. The promoter, 5’UTR and 3’UTR region of the mouse gene are also retained. The chimeric HER3 expression is driven by endogenous mouse Erbb3 promoter, while mouse Erbb3 gene transcription and translation will be disrupted.

Strain specific analysis of HER3 mRNA expression in wild-type B-NDG mice and B-NDG hHER3 mice by RT-PCR. Liver RNA were isolated from wild-type B-NDG mice (+/+) and homozygous B-NDG hHER3 mice (H/H), then cDNA libraries were synthesized by reverse transcription, followed by PCR with mouse or human HER3 primers. Mouse Her3 mRNA was only detectable in wild-type mice. Human HER3 mRNA was exclusively detectable in homozygous B-NDG hHER3 mice but not in wild-type mice.