B6-huKIT Mouse

KIT (also known as c-Kit or CD117) is a type III receptor tyrosine kinase proto-oncogene located on chromosome 4q12, originally identified as the cellular homolog of the feline sarcoma virus v-kit. Upon binding to its ligand stem cell factor (SCF), KIT activates downstream signaling cascades that regulate cellular proliferation, differentiation, migration, and apoptosis ^[1]. KIT plays essential roles in hematopoiesis, stem cell maintenance, gametogenesis, melanogenesis, and mast cell development and function. KIT is prominently expressed in hematopoietic stem cells, mast cells, melanocytes, germ cells (up to the pachytene stage), and interstitial cells of Cajal in the gastrointestinal tract. Its protein product is readily detectable via immunohistochemistry. CD117 is widely used in diagnostic pathology to label tissues such as bone marrow (hematopoietic progenitors), skin (mast cells and melanocytes), gastrointestinal stroma (Cajal cells), and testis (germ cells). Mutations in KIT are implicated in a spectrum of diseases, including gastrointestinal stromal tumors (GIST), systemic mastocytosis, acute myeloid leukemia, seminoma, and vitiligo. These mutations often contribute to the persistence of cancer stem cells and therapeutic resistance ^[1-2]. Clinically approved tyrosine kinase inhibitors (TKIs) such as imatinib, sunitinib, regorafenib, ripretinib, and avapritinib selectively target KIT mutations and are used in the treatment of GIST and mast cell disorders. Ongoing research is advancing next-generation inhibitors, combination therapies, antibody-drug conjugates, and ligand-directed delivery strategies to expand the therapeutic scope of KIT-targeted interventions and support precision medicine approaches ^[3-4].

The B6-huKIT mouse is a humanized model generated by replacing the endogenous murine Kit gene with the human KIT coding sequence via gene editing. This model enables investigation of the molecular pathogenesis of human KIT mutations in relevant disease contexts, preclinical evaluation of TKIs and emerging therapies, and functional studies of KIT in hematopoietic stem cells, melanocytes, and mast cells.