The CALCRL gene encodes a G protein-coupled receptor (GPCR) that forms an active signaling complex for either adrenomedullin or calcitonin gene-related peptide (CGRP), depending on the receptor‘s interaction with RAMP proteins. Interaction of CALCRL with RAMP2 or RAMP3 leads to the formation of a receptor complex that binds ADM, whereas interaction with RAMP1 creates the active form of the CGRP-binding receptor. CGRP is primarily released from sensory nerves and thus is implicated in pain pathways. The proven ability of CGRP antagonists to alleviate migraine has been of most interest in terms of drug development, and knowledge to date concerning this potential therapeutic area is discussed. Other areas covered, where there is less information known on CGRP, include arthritis, skin conditions, diabetes, and obesity. For more ideas, CALCRL-RAMP1 receptor complex is a crucial target for alleviating migraine drugs. Biocytogen developed the B-hCALCRL mice, and the targeting strategy was that the first extramembrane loop of mouse Calcrl was replaced by human homologous, which is responsible for recognition of CGRP. This mouse will become a suitable animal model to evaluate the alleviate migraine drug efficiency.
mRNA and protein expression analysis
Strain specific analysis of CALCRL gene expression in B-CALCRL mice by RT-PCR and western blot. A. Mouse Calcrl mRNA was detectable in lung of wild-type (+/+) mice. Human CALCRL mRNA was detectable only in homozygous B-hCALCRL mice (H/H) but not in wild-type mice. B. Human CALCRL protein was detectable in lung of homozygous B-hCALCRL mice (H/H) and wild type mice,but not in cerebellum. This anti-human CALCRL antibody cross reacts with mouse Calcrl. Taken together, the results suggest that B-hCALCRL mice successfully express human CALCRL.