B6-hHER2(ERBB2) Mice

Catalog Number: C001627

Strain Name: C57BL/6NCya-Erbb2em1(hERBB2)/Cya

Genetic Background: C57BL/6NCya

Reproduction: Homozygote x Homozygote

 

Strain Description

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 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 (aa.25~653) was replaced with the human HER2 extracellular domain (aa.25~652). Homozygous B6-hHER2(ERBB2) mice are viable and fertile. This model can be used for studying the pathological mechanisms and therapeutic approaches of relative cancers, and for the development of HER2-targeted drugs.

Strain Strategy

Figure 1. Gene editing strategy of B6-hHER2(ERBB2) mice. The mouse Erbb2 endogenous extracellular domain (aa.25~653) was replaced with the human ERBB2 extracellular domain (aa.25~652).

 

Application

  • HER2-targeted drug screening, development, and evaluation;
  • Research on the pathological mechanisms and therapeutic approaches of HER2-positive cancers.

 

References
[1]Cheng XQ. A Comprehensive Review of HER2 in Cancer Biology and Therapeutics. Genes. 2024 Jul;15 (7):903.
[2]Zheng-Lin BB, Graham RP, Bekaii-Saab TS. Targeting ERBB2/HER2 genetic alterations: an expanding therapeutic opportunity in gastrointestinal cancers. Chin Clin Oncol. 2023 Oct;12(5):55.
[3]Mirza MB, Choi J, Marincola Smith P, Baechle JJ, Padmanabhan C, Holowatyj AN, Shah SC, Guo X, Idrees K. ERBB2 amplification in gastric cancer: a genomic insight into ethnic disparities. J Natl Cancer Inst. 2024 Nov 1;116(11):1830-1833.
[4]Manrai PA, McHenry A, Sun T, Santin AD, Ratner E, Lin DI, Elvin JA, Hui P, Buza N. Targetable ERBB2/HER2 Mutations in Gynecologic Malignancies: Clinicopathological, Immunohistochemical, and Molecular Correlations. Int J Gynecol Pathol. 2025 Mar 1;44(2):144-154.