Rgs7bp-KO Mouse

Rgs7bp, also known as R7bp, is a palmitoylated membrane-anchoring protein. It facilitates Gαi/o-directed GTPase activating protein activity mediated by the Gβ5/R7-RGS complex. This protein is expressed in neurons and is involved in G-protein-coupled receptor (GPCR) signaling, which is fundamental to numerous physiological functions [3,5,6].

Knockout of R7bp in mice diminishes scratching responses to multiple pruritogens, indicating its key role in the regulation of itch sensation. This suggests that targeting R7bp-dependent GTPase activating protein activity could be a novel therapeutic strategy for pathological itch [3]. In asthmatic patients, a haplotype of block 3 of the RGS7BP gene was associated with aspirin-exacerbated respiratory disease (AERD), and the haplotype may play a protective role against aspirin hypersensitivity in asthma, perhaps by altering the responsiveness of muscarinic receptors [1]. In a study of tuberculosis severity, SNPs in the introns of RGS7BP were associated with clinically meaningful reductions in disease severity, and RGS7BP is highly expressed in blood vessels and plays a role in infectious disease pathogenesis [2]. Also, in a diverse sample of U.S. Army soldiers, RGS7BP was among the genes with variants enriched in individuals with a history of suicide attempt, and brains from suicide-deceased individuals aberrantly expressed RGS7BP [4].

In conclusion, Rgs7bp plays essential roles in itch sensation, asthma-related aspirin intolerance, tuberculosis severity, and potentially in suicide-related behaviors. Gene knockout models in mice have been crucial in uncovering its role in itch regulation. These findings contribute to our understanding of the biological functions of Rgs7bp and its implications in multiple disease areas.

References:

1. Lee, Eun Hee, Park, Byung Lae, Park, Se-Min, Shin, Hyoung Doo, Park, Choon-Sik. 2011. Association analysis of RGS7BP gene polymorphisms with aspirin intolerance in asthmatic patients. In Annals of allergy, asthma & immunology : official publication of the American College of Allergy, Asthma, & Immunology, 106, 292-300.e6. doi:10.1016/j.anai.2010.10.021. https://pubmed.ncbi.nlm.nih.gov/21457877/

2. McHenry, Michael L, Simmons, Jason, Hong, Hyejeong, Williams, Scott M, Stein, Catherine M. 2023. Tuberculosis severity associates with variants and eQTLs related to vascular biology and infection-induced inflammation. In PLoS genetics, 19, e1010387. doi:10.1371/journal.pgen.1010387. https://pubmed.ncbi.nlm.nih.gov/36972313/

3. Pandey, Mritunjay, Zhang, Jian-Hua, Mishra, Santosh K, Hoon, Mark A, Simonds, William F. . A central role for R7bp in the regulation of itch sensation. In Pain, 158, 931-944. doi:10.1097/j.pain.0000000000000860. https://pubmed.ncbi.nlm.nih.gov/28134655/

4. Wilkerson, Matthew D, Hupalo, Daniel, Gray, Joshua C, Ursano, Robert J, Stein, Murray B. 2023. Uncommon Protein-Coding Variants Associated With Suicide Attempt in a Diverse Sample of U.S. Army Soldiers. In Biological psychiatry, 96, 15-25. doi:10.1016/j.biopsych.2023.12.008. https://pubmed.ncbi.nlm.nih.gov/38141912/

5. Stoveken, Hannah M, Fernandez-Vega, Virneliz, Muntean, Brian S, Spicer, Timothy P, Martemyanov, Kirill A. 2021. Identification of Potential Modulators of the RGS7/Gβ5/R7BP Complex. In SLAS discovery : advancing life sciences R & D, 26, 1177-1188. doi:10.1177/24725552211020679. https://pubmed.ncbi.nlm.nih.gov/34112017/

6. Patil, Dipak N, Rangarajan, Erumbi S, Novick, Scott J, Izard, Tina, Martemyanov, Kirill A. 2018. Structural organization of a major neuronal G protein regulator, the RGS7-Gβ5-R7BP complex. In eLife, 7, . doi:10.7554/eLife.42150. https://pubmed.ncbi.nlm.nih.gov/30540250/