The CD86 gene (Cluster of Differentiation 86) encodes a critical type I transmembrane glycoprotein that serves as a potent costimulatory ligand in the adaptive immune response. Primarily expressed on the surface of antigen-presenting cells (APCs)—including activated B cells, macrophages, and dendritic cells—the CD86 protein (also known as B7-2) acts as a ligand for two distinct receptors on T cells: the stimulatory receptor CD28 and the inhibitory receptor CTLA-4 ^[1]. Its primary function is to provide the "second signal" necessary for T cell activation, proliferation, and cytokine production following the initial recognition of an antigen. Beyond lymphoid tissues, CD86 labeling is a hallmark of activated myeloid lineages and is often used to characterize M1-polarized macrophages ^[2]. Dysregulation of the CD86 pathway is significantly associated with various autoimmune diseases, such as systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA), as well as the immune evasion mechanisms observed in several types of hematologic malignancies and solid tumors ^[3]. The huCD86 mouse model was generated by replacing the endogenous extracellular domain of mouse Cd86 with the extracellular domain of human CD86, while retaining the mouse signal peptide and aa.245~309. This model is suitable for the study of various autoimmune diseases—including systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA)—as well as multiple malignancies, and for the development of CD86-targeted therapeutics.

The CRLF2 (Cytokine Receptor Like Factor 2) gene encodes a type I cytokine receptor protein also known as the thymic stromal lymphopoietin receptor (TSLPR). This protein primarily functions by forming a heterodimeric complex with the interleukin-7 receptor alpha (IL7Rα), which, upon binding its ligand TSLP, activates the JAK/STAT (specifically JAK2, STAT3, and STAT5) and PI3K/AKT/mTOR signaling pathways to regulate hematopoietic cell proliferation, development, and immune homeostasis ^[1]. While physiological expression is most prominently labeled in lymphoid and myeloid-related tissues—including the bone marrow, thymus, spleen, and lungs, as well as specific cell types like dendritic cells, mast cells, and B-cell progenitors—it is also detected in the intestine and testis. Clinically, genetic rearrangements such as the P2RY8-CRLF2 fusion or IGH-CRLF2 translocation lead to CRLF2 overexpression, which is a hallmark of high-risk B-cell precursor acute lymphoblastic leukemia (B-ALL), particularly in children with Down syndrome ^[2]. Beyond oncology, dysregulated CRLF2 signaling is heavily implicated in inflammatory and allergic diseases, such as asthma and allergic rhinitis, where it drives Th2-mediated immune responses ^[3]. The hTSLPR mouse is a humanized model constructed through gene-editing technology, in which part of exon 1 to intron 7 of Mouse Crlf2 is replaced with Human CRLF2 CDS-Mouse Crlf2 CDS cassette. This model is applicable to research on B-cell precursor acute lymphoblastic leukemia (B-ALL) and inflammatory diseases, including asthma and allergic rhinitis. Furthermore, it supports the screening, development, and preclinical evaluation of TSLPR-targeted therapeutics.

Adra1a is located on chromosome 14 of mice. Nuclease Technology was used to design sgRNA; Adra1a knockout mice were obtained by applying high-throughput electroporation of fertilized eggs. After sexual maturity, sperm were collected for cryopreservation.

Vmn1r50 is located on chromosome 6 of mice. SgRNA and ssDNA will be designed using Nuclease Technology; Vmn1r50 conditional knockout mice will be obtained by high-throughput electroporation of fertilized eggs. After sexual maturity, sperm will be collected for cryopreservation.