Gprc5c-flox Mouse

Gprc5c, an orphan G protein-coupled receptor belonging to the class C GPCR family, has diverse functions. It is involved in regulating hematopoietic stem cell (HSC) dormancy, and its associated pathways may include those related to NF-κB activation, cilia composition regulation, smooth muscle contraction, and saccharide sensing. It plays a significant role in various biological processes and diseases [4,5].

In acute myeloid leukemia (AML), high Gprc5c levels in patient cohorts correlated with poorer survival. Ectopic Gprc5c expression increased AML aggression through NF-κB activation, altering metabolism with increased intracellular branched-chain amino acids (BCAAs). Loss of Gprc5c reversed this onco-metabolic profile and abrogated leukemia-initiating potential [1].

In olfactory neurons, Gprc5c deficiency altered sensory cilia structure, increased ciliary layer thickness, and changed the localization of olfactory signalling proteins, leading to increased neuronal activity and improved smell-based food detection in knockout mice [2].

In smooth muscle cells, tamoxifen-inducible, SMC-specific Gprc5c knockout mice showed reduced angiotensin II-dependent calcium mobilization, contraction, and arterial hypertension. Knockdown of Gprc5c in human aortic SMC diminished Ang II-dependent inositol phosphate production and myosin light chain phosphorylation [3].

In the kidney, Gprc5c KO mice had altered acid-base homeostasis, with lower blood pH and higher urine pH. Gprc5c internalization was triggered by alkaline extracellular pH, and it increased Na+/H+ exchanger 3 (NHE3) activity at alkaline pH, which was reduced in Gprc5c KO mice [6].

In summary, Gprc5c has essential functions in multiple biological processes. Its role in HSC dormancy, AML, olfactory function, smooth muscle contraction, and renal acid-base regulation has been revealed through gene knockout mouse models. These findings contribute to understanding the mechanisms of related diseases and may provide potential therapeutic targets for diseases such as AML and arterial hypertension.