Knockout Mouse Models for GPCRs

 

 

Our catalog of KO mice contains numerous models targeting G-protein coupled receptors (GPCRs), the largest family of druggable molecular targets.

All our lines are submitted to a panel of phenotyping tests mandated by the International Mouse Phenotyping Consortium (IMPC) and systematically performed to identify significant phenotypes between WT and KO.

Examples of phenotyped KO lines for GPCRs:

Ackr3, Adar, Adgra1, Adgrb1, Cxcr1, Cxcr2, F2rl1, Ffar2, Gpr1, Gpr152, Gpr33, Pth1r, Rxfp2, Tmem181a…

 

Example 1:

KO mice for thrombin receptor-like F2rl1, whose activation is linked to neuronal activation and increased intestinal permeability (1), show significant differences with WT in 3 tests performed under the IMPC guidelines, including:

a) Decreased prepulse inhibition (assessed by acoustic startle and pre-pulse inhibition)

Figure 1a - KO mice for thrombin receptor-like F2rl1

b) Increased circulating HDL cholesterol level (assessed by clinical blood chemistry)

Figure 1b - KO mice for thrombin receptor-like F2rl1

Example 2:

Mutations in the human relaxin/insulin-like family peptide receptor RXFP2 are associated with cryptorchidism (2). KO mice for their murine homolog Rxfp2 show significant differences with WT in 18 tests performed under the IMPC guidelines, including:

a) Increased hemoglobin content (assessed by hematology)

Figure 2a - RXFP2 KO associated with cryptorchidism

b) Decreased body weight

Figure 2b - RXFP2 KO associated with cryptorchidism

Figure 2c - RXFP2 KO associated with cryptorchidism

c) Expression data are also available for some lines, including Rxfp2-/+ mice, showing LacZ expression in the testis.

References:

  1. Ramachandran, R., Noorbakhsh, F., DeFea, K. & Hollenberg, M. D. Targeting proteinase-activated receptors: therapeutic potential and challenges. Nat. Rev. Drug Discov. 11, 69–86 (2012).
  2. Gorlov, I. P. et al. Mutations of the GREAT gene cause cryptorchidism. Hum Mol Genet 11, 2309–2318 (2002).