Epidermal growth factor receptor 2 (ERBB2), also known as HER2 or Neu protein, encoded by the ERBB2 gene, is a member of the ErbB receptor tyrosine kinase family. ERBB2 gene expression is subject to complex regulation, influenced by diverse transcription factors and signaling pathways, and is normally expressed at low levels in various epithelial tissues, including the breast, ovary, and gastrointestinal tract ^[1]. HER2, a transmembrane receptor tyrosine kinase, functions at the cell surface, primarily through heterodimerization with other epidermal growth factor receptor family members, such as HER3. This activation initiates downstream signaling pathways, including PI3K/Akt and MAPK, which regulate cell growth, proliferation, differentiation, and migration ^[1]. In tumor tissues, ERBB2 gene amplification or overexpression is frequently observed, particularly in solid tumors such as breast, gastric, and ovarian cancers. Elevated HER2 expression is strongly associated with tumorigenesis, progression, invasion, metastasis, and poor patient prognosis, establishing it as a key prognostic marker and therapeutic target in breast and other cancers ^[2-4]. Targeted therapies against HER2, including monoclonal antibodies such as trastuzumab and pertuzumab, and small molecule tyrosine kinase inhibitors, have become essential treatments for patients with HER2-positive breast cancer and other malignancies ^[4].

The B6-hHER2(ERBB2) mouse is a humanized model constructed using gene editing technology, where the mouse HER2 extracellular domain was replaced with the human HER2 extracellular domain. Homozygous B6-hHER2(ERBB2) mice are viable and fertile. This model can be used for studying the pathological mechanisms and therapeutic approaches of related cancers, and for the development of HER2-targeted drugs.