Calcitonin receptor-like receptor (CALCRL) is a seven-transmembrane G protein-coupled receptor encoded by the CALCRL gene. It mediates the pleiotropic effects of calcitonin gene-related peptide (CGRP) and adrenal medullary peptide (ADM), two structurally related neuropeptides that are potent vasodilators and play an important role in blood pressure regulation ^[1]. In addition, CALCRL is involved in various other biological processes, including cell proliferation, cell death regulation, vascular biology, and inflammation ^[2]. CALCRL is currently being investigated as a new target for the treatment of migraine ^[3]. In solid tumors, antibodies that target CALCRL have been shown to reduce tumor growth by either disrupting angiogenesis or by directly inhibiting cancer cell proliferation ^[4]. CALCRL is also expressed in normal CD34+ hematopoietic progenitor cells, and CGRP and ADM can directly stimulate these cells to form colonies in vitro, suggesting a role for CALCRL in physiological bone marrow generation ^[5]. This strain represents a humanized mouse model of the Calcrl gene. Using gene editing technology, the sequence encoding the extracellular domain of the mouse Calcrl gene was replaced with the corresponding sequence from the human CALCRL gene. This model can be used to study the mechanisms of various physiological and pathological processes, such as blood pressure regulation, cell proliferation, cell death, vascular biology, physiological bone marrow generation, inflammation, and tumor growth, as well as the development of CALCRL-targeted migraine drugs and therapies. Homozygous B6-hCALCRL mice are viable and fertile.

Dkkl1 is located on chromosome 7 of mice. Nuclease Technology will be used to design sgRNA; Dkkl1 knockout mice will be obtained by applying high-throughput electroporation of fertilized eggs. After sexual maturity, sperm were collected for cryopreservation.