Gpr153-KO Mouse

Gpr153, an orphan G-protein-coupled receptor, belongs to the Rhodopsin (class A) family of GPCRs. It may potentially interact with adrenalin and noradrenalin based on phylogenetic analysis [1]. Gpr153 is widely expressed in the central nervous system and peripheral tissues, with high expression in the thalamus, cerebellum, and arcuate nucleus [3]. In the anterior pituitary of heifers, it is expressed in gonadotrophs, colocalizing with gonadotropin-releasing hormone receptor (GnRHR) in the plasma membrane, and its expression changes in a stage-dependent manner during the reproductive cycle [2].

Phylogenetic and synteny analyses suggest Gpr153 shares a common ancestor with Gpr162 likely through a duplication event before the divergence of tetrapods and the teleost lineage [3]. In heifers, its expression in the anterior pituitary is stage-dependent during the reproductive cycle, which may imply its role in regulating reproduction [2]. Additionally, in bovine gonadotrophs, Gpr153 co-localizes with the GnRH receptor in lipid rafts on the cell surface, potentially regulating luteinizing hormone and follicle-stimulating hormone secretion [5]. In Wistar rats, the expression of Gpr153 in the kidney is altered in diabetic nephropathy, suggesting its possible involvement in this disease [4]. In sporadic cases of childhood-onset schizophrenia, Gpr153 has been identified as a candidate gene due to de novo variants found in affected probands [6].

In summary, Gpr153 has diverse functions. It is involved in the regulation of reproduction, potentially through its interaction with GnRH-related pathways in heifers. Its altered expression in diabetic nephropathy and its candidacy as a gene in childhood-onset schizophrenia indicate its significance in these disease conditions. The study of Gpr153 in different animal models helps in understanding its biological functions and its implications in various diseases.

References:

1. Kakarala, Kavita Kumari, Jamil, Kaiser. 2014. Sequence-structure based phylogeny of GPCR Class A Rhodopsin receptors. In Molecular phylogenetics and evolution, 74, 66-96. doi:10.1016/j.ympev.2014.01.022. https://pubmed.ncbi.nlm.nih.gov/24503482/

2. Pandey, Kiran, Kereilwe, Onalenna, Kadokawa, Hiroya. 2017. Heifers express G-protein coupled receptor 153 in anterior pituitary gonadotrophs in stage-dependent manner. In Animal science journal = Nihon chikusan Gakkaiho, 89, 60-71. doi:10.1111/asj.12920. https://pubmed.ncbi.nlm.nih.gov/28960688/

3. Sreedharan, Smitha, Almén, Markus S, Carlini, Valeria P, Fredriksson, Robert, Schiöth, Helgi B. 2011. The G protein coupled receptor Gpr153 shares common evolutionary origin with Gpr162 and is highly expressed in central regions including the thalamus, cerebellum and the arcuate nucleus. In The FEBS journal, 278, 4881-94. doi:10.1111/j.1742-4658.2011.08388.x. https://pubmed.ncbi.nlm.nih.gov/21981325/

4. Ruiz-Hernández, A, Cabrera-Becerra, S, Vera-Juárez, G, Arauz, J, Villafaña, S. 2020. Diabetic nephropathy produces alterations in the tissue expression profile of the orphan receptors GPR149, GPR153, GPR176, TAAR3, TAAR5 and TAAR9 in Wistar rats. In Nucleosides, nucleotides & nucleic acids, 39, 1150-1161. doi:10.1080/15257770.2020.1780437. https://pubmed.ncbi.nlm.nih.gov/32643557/

5. Kadokawa, Hiroya. 2020. Discovery of new receptors regulating luteinizing hormone and follicle-stimulating hormone secretion by bovine gonadotrophs to explore a new paradigm for mechanisms regulating reproduction. In The Journal of reproduction and development, 66, 291-297. doi:10.1262/jrd.2020-012. https://pubmed.ncbi.nlm.nih.gov/32249236/

6. Ambalavanan, Amirthagowri, Girard, Simon L, Ahn, Kwangmi, Rapoport, Judith, Rouleau, Guy A. 2015. De novo variants in sporadic cases of childhood onset schizophrenia. In European journal of human genetics : EJHG, 24, 944-8. doi:10.1038/ejhg.2015.218. https://pubmed.ncbi.nlm.nih.gov/26508570/