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.