Lrrc19-flox 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 and induces production of pro-inflammatory cytokines, playing a role in innate immune responses, especially in tissues like the kidney [3].

In Lrrc19 knockout (KO) mice, several phenotypes were observed. In the gut, Lrrc19 KO mice had a tighter junction and narrower gaps in colon epithelium cells, with lower levels of serum lipopolysaccharide and 4 kDa-fluorescein isothiocyanate-dextran after gavage, indicating that Lrrc19 promotes gut epithelial barrier permeability by degrading PKC-ζ and PKCι/λ to reduce the expression of ZO-1, ZO-3, and occludin [1]. Lrrc19-deficient mice were also more susceptible to uropathogenic Escherichia coli (UPEC) infection as recognition of UPEC by Lrrc19 induces cytokine, chemokine, and antimicrobial substance production through TRAF2-and TRAF6-mediated NF-κB and MAPK signalling pathways [2]. In addition, knockdown of Lrrc19 in a mouse ulcer model alleviated disease severity, immune cell infiltration, and pro-inflammatory cytokines production, suggesting it promotes NFκB-dependent pro-inflammatory response in ischemia-reperfusion (I/R)-induced tissue damage [4]. Maternal high-fat diet up-regulated Lrrc19 expression in offspring, disrupting the intestinal mucus barrier, while Lrrc19 deletion alleviated this disruption [5].

In conclusion, Lrrc19 is crucial in multiple biological processes. Its KO models have revealed its role in gut epithelial barrier function, response to uropathogenic bacteria in the kidney, and in pressure ulcer-related inflammation. These findings suggest Lrrc19 could be a potential therapeutic target in related disease areas, such as gut-related disorders, urinary tract infections, and pressure ulcers.