huRAMP2 Mouse

The RAMP2 gene, a member of the RAMP family, encodes a single‑pass transmembrane protein. RAMP2 is widely expressed in various tissues, with higher expression levels observed in the lung, vascular endothelial cells, heart, placenta, and fetal tissues, and is also detectable in immune‑related cells ^[1]. This protein forms a heterodimer with the calcitonin receptor‑like receptor (CRLR/CALCRL), constituting the specific receptor for adrenomedullin (AM), i.e., the AM1 receptor. It is involved in regulating receptor trafficking to the plasma membrane, core glycosylation, and ligand‑binding specificity, and activates downstream signaling pathways such as cAMP, thereby playing key roles in angiogenesis, vascular integrity maintenance, lymphatic development, cardiovascular homeostasis, and placental function ^[2-3]. Additionally, RAMP2 can form a complex with the calcitonin receptor (CALCR) and participate in the regulation of placental and other tissue functions. Dysregulation of RAMP2 expression or function is closely associated with multiple diseases. Heterozygous mutations or functional impairment can disrupt the AM‑RAMP2/CLR‑cAMP axis, leading to retinal ganglion cell death and subsequently primary open‑angle glaucoma (POAG) ^[4]. RAMP2 deficiency is also linked to vascular hyperpermeability, impaired angiogenesis, placental dysfunction, dilated cardiomyopathy‑like phenotypes, and endocrine abnormalities, and may promote tumor metastasis by disrupting vascular homeostasis and inducing an inflammatory microenvironment ^[5]. Moreover, RAMP2 exerts a protective role in the pathogenesis of acute respiratory distress syndrome (ARDS) by maintaining pulmonary vascular endothelial barrier function ^[6].

The huRAMP2 mouse is a humanized model generated via gene editing technology, in which the mouse Ramp2 endogenous signal peptide and extracellular domain were replaced with the human RAMP2 signal peptide and extracellular domain. This model is applicable to mechanistic studies of diseases such as acute respiratory distress syndrome (ARDS) and primary open‑angle glaucoma (POAG), and also serves as a platform for the screening, development, and preclinical in vivo evaluation of therapeutic agents targeting the AM‑RAMP2 system.