Plcb3-flox Mouse

Plcb3, or Phosphoinositide phospholipase C-beta-3, is an enzyme that converts phosphatidylinositol 4,5 bisphosphate (PIP2) to inositol 1,4,5 triphosphate (IP3) and diacylglycerol, playing a key role in phosphoinositide signalling [4]. It is involved in multiple biological processes and pathways, such as being a key player in hyperkeratosis [1], and is associated with Toll-like receptor's inflammatory signaling cascade in cystic fibrosis bronchial epithelial cells [2].

A homozygous loss-of-function variant in Plcb3 causes a new form of spondylometaphyseal dysplasia with corneal dystrophy and developmental delay (SMDCD), as it disrupts the binding of a key element to the catalytic core, destabilizes Plcb3, and leads to elevated PIP2 levels in patient fibroblasts, causing F-actin cytoskeleton disorganisation [4]. In cystic fibrosis, the c.2534C>T (p.S845L) loss-of-function variant of Plcb3 reduces Pseudomonas aeruginosa -dependent IL-8 release from bronchial epithelial cells, indicating its role in modulating the inflammatory response [2]. In colorectal cancer, high expression of Plcb3 is correlated with poorer prognosis, and its knockdown inhibits cell progression. Cetuximab treatment reduces both β-catenin and Plcb3 expression, suggesting Plcb3's role in promoting cetuximab-mediated inhibition of the Wnt/β-catenin signaling pathway [3].

In conclusion, Plcb3 is essential in phosphoinositide signalling and is associated with various diseases. Its role in conditions like SMDCD, cystic fibrosis, and colorectal cancer has been revealed through functional studies, highlighting its significance in understanding disease mechanisms. The findings from these studies contribute to the exploration of potential therapeutic targets related to these diseases.