Lrrc19-KO Mouse

Lrrc19, leucine-rich repeat-containing protein 19, is a transmembrane protein belonging to the LRR protein family. Its central core has four LRR repeating modules and a casein kinase (CK2) phosphorylation site in the cytoplasmic domain. It activates NF-κB, induces production of pro-inflammatory cytokines, and is involved in innate immune responses [3]. It also has a role in maintaining the integrity of the gut epithelial barrier and in preventing uropathogenic bacteria infection in the kidney [1,2].

In Lrrc19 knockout (KO) mice, the gut epithelial barrier is more intact, with a tighter junction and narrower gaps in colon epithelium cells. There are lower levels of serum lipopolysaccharide and 4 kDa-fluorescein isothiocyanate-dextran after gavage, indicating reduced gut permeability. This is due to Lrrc19 degrading PKC-ζ and PKCι/λ, which reduces the expression of ZO-1, ZO-3, and occludin [1]. Lrrc19-deficient mice are also more susceptible to uropathogenic Escherichia coli (UPEC) infection, as recognition of UPEC by Lrrc19 in normal mice induces cytokine, chemokine, and antimicrobial substance production through TRAF2-and TRAF6-mediated NF-κB and MAPK signalling pathways [2]. In maternal high-fat diet (MHFD) studies, Lrrc19 deletion alleviated the disruption of the intestinal mucus barrier in offspring, with gut microbiota and metabolite imbalances restored [4].

In conclusion, Lrrc19 plays essential roles in the innate immune response, gut epithelial barrier function, and prevention of uropathogenic bacteria infection. The use of Lrrc19 KO mouse models has provided valuable insights into its role in maintaining gut and kidney homeostasis, as well as in understanding how diet-related factors like MHFD can impact these functions through Lrrc19-mediated mechanisms.