• Gene Information: HER2 (Human Epidermal Growth Factor Receptor 2), also known as ERBB2, is a member of the ERBB receptor family encoded on human chromosome 17. It is a well-established oncogenic driver and therapeutic target in multiple cancers. 
• Protein Expression: HER2 is expressed at low levels in normal epithelial tissues but is amplified or overexpressed in various cancers, particularly breast and gastric cancers. Its overexpression is associated with aggressive tumor progression. 
• Signaling Pathway: HER2 forms homo- or heterodimers with other ERBB family members, activating downstream PI3K/AKT, MAPK, and other signaling pathways that promote cell growth and survival.
•  Model application : Targeting HER2 with monoclonal antibodies, ADCs, tyrosine kinase inhibitors, and bispecific antibodies can block HER2 signaling and eliminate HER2-expressing tumor cells.

HER2 

• The exons 2-17 of mouse Erbb2 gene that encode extracellular domain and transmembrane domain were replaced by human counterparts in B-NDG hHER2 mice. The genomic region of mouse Erbb2 gene that encodes cytoplasmic portion was retained. 
• The promoter, 5’UTR and 3’UTR region of the Erbb2 gene were also retained. The chimeric ERBB2 expression was driven by endogenous mouse Erbb2 promoter, while mouse Erbb2 gene transcription and translation will be disrupted.

Strain specific analysis of HER2 mRNA expression in wild-type B-NDG mice and homozygous B-NDG hHER2 mice by RT-PCR. Liver, lung and stomach RNA were isolated from wild-type B-NDG mice (+/+) and homozygous B-NDG hHER2 mice (H/H), then cDNA libraries were synthesized by reverse transcription, followed by PCR with mouse or human HER2 primers. Sequencing of the PCR products confirmed that the amplified sequences were consistent with database reference sequences.

Immunohistochemical (IHC) analysis of HER2 protein expression in wild-type mice and B-NDG hHER2 mice. Thirteen major tissues were collected from wild-type mice and homozygous B-NDG hHER2 mice and analyzed by IHC with anti-mouse HER2 antibodies (ab214275) and anti-human HER2 antibodies (ab16662). Mouse HER2 was detected in the lung, liver, stomach, colon, small intestine, uterus and breast of wild-type mice (Figure 1). Human HER2 was detected in the lung, liver, stomach, colon, small intestine, uterus, breast and kidney of homozygous B-NDG hHER2 mice (Figure 2).