The IL5RA gene encodes the interleukin-5 receptor subunit alpha (IL5RA), the receptor subunit that specifically binds IL5. It is primarily expressed on eosinophils, basophils, and their progenitor cells, with low expression levels in most normal tissues ^[1]. IL5RA plays a critical role in the proliferation, differentiation, survival, recruitment, and activation of eosinophils. Upon binding to IL5, it activates downstream signaling pathways such as JAK2-STAT5, thereby promoting type 2 inflammatory responses. Excessive activation of the IL5/IL5RA axis in cells or tissues can lead to eosinophil expansion and tissue infiltration, exacerbating inflammation and tissue damage ^[2]. IL5RA exerts a central regulatory role in the pathogenesis of eosinophil-related inflammatory diseases, including severe eosinophilic asthma (SEA), chronic rhinosinusitis with nasal polyps (CRSwNP), and eosinophilic granulomatosis with polyangiitis (EGPA) ^[3-5]. Studies have shown that abnormal IL5RA expression is causally associated with the genetic risk of multiple myeloma (MM), positioning it as a potential tumor biomarker and therapeutic target ^[6]. Humanized anti-IL5RA CAR-T cell therapy can effectively deplete eosinophils and their precursors at various developmental stages in the bone marrow and peripheral blood ^[1]. Currently, multiple clinical drugs targeting the IL-5/IL5RA pathway have been approved or are under development, including mepolizumab, reslizumab, and benralizumab ^[7-8]. The huIL5RA mouse was generated by replacing the mouse Il5ra endogenous extracellular domain with the human IL5RA extracellular domain. The murine transmembrane-cytoplasmic region was preserved. huIL5RA mice can be used for the research and development as well as preclinical pharmacological and efficacy evaluation of IL5RA-targeted drugs for multiple eosinophil-related inflammatory diseases, including severe eosinophilic asthma (SEA), chronic rhinosinusitis with nasal polyps (CRSwNP), and eosinophilic granulomatosis with polyangiitis (EGPA), as well as multiple myeloma (MM).

Pck1 is located on chromosome 2 of mice. Nuclease Technology was used to design sgRNA; Pck1 knockout mice were obtained by applying high-throughput electroporation of fertilized eggs. After sexual maturity, sperm were collected for cryopreservation.

Galnt10 is located on chromosome 11 of mice. SgRNA and ssDNA will be designed using Nuclease Technology; Galnt10 conditional knockout mice will be obtained by high-throughput electroporation of fertilized eggs. After sexual maturity, sperm will be collected for cryopreservation.