Constitutive knockout of Gpr21 inhibits the ex vivo migration of mouse immune cells

Research output: Contribution to conferenceAbstract

Abstract

Through immune cell infiltration into adipose tissue, chronic low-grade inflammation can develop and play a key role in the pathogenesis of obesity-induced insulin resistance1. Insight into the mechanistic link between insulin resistance and inflammation has revealed the activation of various inflammatory receptors and signalling pathways. One such receptor is the orphan G protein-coupled receptor (GPCR), GPR21. Two independent studies show Deltagen Gpr21-/- mice have improved glucose tolerance and systemic insulin sensitivity compared with wild-type controls2,3, primarily due to a reduction in tissue inflammation caused by impaired migratory capability of monocytes and macrophages into adipose tissue. However, during this study it was revealed that the Gpr21 gene resides within the intron of the RAB GTPase activating protein 1 (Rabgap1) gene, which is also disrupted in the Deltagen Gpr21-/- mice4, making it unclear as to which gene might be responsible for the effects. Due to this controversy we developed a new Gpr21 knockout strain, using clustered regularly interspaced short palindromic repeats (Crispr) technology. Gene expression analysis of metabolic tissues from these Crispr animals, including the liver, adipose and spleen, revealed no effect on the Rabgap1 gene. Using bone marrow monocytes and intraperitoneal macrophages isolated from 8-week old Deltagen Gpr21-/- and Crispr Gpr21-/- animals fed normal chow, we observed the complete loss in the migratory capability of these cell types, compared to wild-type, in response to monocyte chemoattractant protein-1 (MCP-1) and leukotriene B4 (LTB4). These data indicate that GPR21 is involved in the chemotaxis of immune cells, however, the effect of a high fat diet is necessary to fully ascertain the importance of these findings. Targeting this receptor may prove beneficial for the treatment of type 2 diabetes and its complications including non-alcoholic fatty liver disease and steatohepatitis (NAFLD/NASH).
Original languageEnglish
Publication statusPublished - 2017
EventAustralian Diabetes Society (ADS) and the Australian Diabetes Educators Association (ADEA) Annual Scientific Meeting 2017: Bioscientific Symposium - Practical Publishing Advice

- Perth, Perth, Australia
Duration: 30 Aug 20171 Sep 2017

Conference

ConferenceAustralian Diabetes Society (ADS) and the Australian Diabetes Educators Association (ADEA) Annual Scientific Meeting 2017: Bioscientific Symposium - Practical Publishing Advice

CountryAustralia
CityPerth
Period30/08/171/09/17

Cite this

Riddy, D., Simonds, S., Bosnyak-Gladovic, S., Fabb, S., Rueda, P., Sexton, P. M., Summers, R., Cowley, M., & Langmead, C. (2017). Constitutive knockout of Gpr21 inhibits the ex vivo migration of mouse immune cells. Abstract from Australian Diabetes Society (ADS) and the Australian Diabetes Educators Association (ADEA) Annual Scientific Meeting 2017: Bioscientific Symposium - Practical Publishing Advice

, Perth, Australia.