Prokr1-flox Mouse

Prokr1, short for prokineticin receptor 1, is a G protein-coupled receptor. It is involved in various metabolic functions, and its signaling is associated with pathways like Gs-mediated phosphorylation of cyclic adenosine monophosphate (cAMP) response element-binding protein (CREB), which in turn affects the expression of genes such as nuclear receptor subfamily 4 group A member 2 (NR4A2) [1]. It also activates Gq-mediated PI3K/AKT and MAPK/ERK signaling pathways in skeletal muscle cells [2].

In Prokr1-deficient mice, there are unfavorable metabolic phenotypes including lower lean mass, enlarged muscle fibers, impaired glucose and insulin tolerance, reduced energy expenditure and exercise performance. The deletion also leads to decreased oxidative muscle fiber composition and reduced activity in the Prokr1-CREB-Nr4a2 pathway, which can be restored by AAV-mediated Prokr1 rescue [1]. In addition, in diet-induced obese mice, the mRNA and protein levels of Prokr1 were significantly decreased in skeletal muscle and white adipose tissue [2].

In conclusion, Prokr1 plays a crucial role in metabolic functions, especially in regulating oxidative muscle fiber specification and insulin sensitivity in skeletal muscle. The use of Prokr1-deficient mouse models has revealed its importance in these biological processes and its potential as a therapeutic target for metabolic disorders and muscular-metabolic diseases [1,2].