Pigg-flox Mouse

PIGG, Phosphatidylinositol Glycan Anchor Biosynthesis, class G, is an ethanolamine phosphate transferase. It catalyzes the modification of glycosylphosphatidylinositol (GPI), which serves as an anchor on the cell membrane for GPI-anchored proteins (GPI-APs). The GPI-anchor biosynthesis pathway in which PIGG is involved is crucial for the proper localization and function of numerous cell-surface proteins [1,2].

Pathogenic variants in PIGG have been found to cause inherited GPI deficiency (IGD). In in vitro studies using a PIGG/PIGO double knockout system, enzymatic activity defects for PIGG variants were demonstrated [1]. Patients with biallelic PIGG variants show a range of phenotypes. Those with null or severely decreased PIGG activity present with classic IGD symptoms like hypotonia, intellectual disability/developmental delay, seizures, along with cerebellar atrophy, various neurological manifestations, and mitochondrial dysfunction [1]. Patients with mildly decreased activity show autism spectrum disorder [1]. Additionally, recessive variants in PIGG can cause a motor neuropathy with variable conduction block, childhood tremor, and febrile seizures [3]. PIGG has also been associated with the Emm blood group system, as rare PIGG deficiencies are linked to the Emm-phenotype [2].

In conclusion, PIGG is essential for GPI-anchor biosynthesis, and its proper function is crucial for normal cellular processes. Studies, especially those using gene knockout-like models in vitro, have revealed its role in various disease conditions such as IGD, motor neuropathy, and potentially in the context of the Emm blood group system. Understanding PIGG's function provides insights into the pathogenesis of these associated disorders.