PIGT Antibody
Description
Introduction to PIGT and PIGT Antibodies
The PIGT gene encodes the glycosylphosphatidylinositol (GPI) transamidase component PIG-T, a critical enzyme in the biosynthesis of GPI anchors. These anchors attach proteins to cell membranes, enabling roles in cell adhesion, signaling, and immune protection . PIGT antibodies are specialized reagents targeting the PIGT protein or GPI-anchored molecules. They are pivotal in diagnosing genetic disorders (e.g., paroxysmal nocturnal hemoglobinuria, PNH) and studying GPI biosynthesis deficiencies .
Research Applications of PIGT Antibodies
PIGT antibodies are utilized across diverse experimental workflows:
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Flow Cytometry: Detection of GPI-anchored proteins (e.g., CD16, CD24) on cell surfaces. For instance, flow cytometry revealed CD16 levels at 16.92% and CD24 at 22.16% in a PIGT-mutant patient compared to controls .
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Western Blot: Validation of PIGT protein expression. Antibodies like ab80888 (Abcam) and PPIG Antibody #3803 (Cell Signaling Technology) detect endogenous PIGT at ~110 kDa .
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ELISA and Immunohistochemistry: Quantification of GPI-anchored proteins in serum or tissues .
Role in Genetic Disorders
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Paroxysmal Nocturnal Hemoglobinuria (PNH): Biallelic PIGT mutations (germline + somatic) disrupt GPI anchoring, leading to hemolytic anemia and recurrent inflammation .
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Multiple Congenital Anomalies-Hypotonia-Seizures Syndrome 3 (MCAHS3): Homozygous PIGT variants (e.g., c.550G>A) correlate with severe neurodevelopmental deficits and reduced CD16/CD24 expression .
Mechanistic Insights
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GPI Transamidase Stability: PIGT mutations destabilize the GPI transamidase complex, impairing protein anchoring .
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Feedback Regulation: Elevated PIGT mRNA levels in mutant cells suggest compensatory mechanisms, though functional rescue is absent .
Table 1: GPI-Anchored Protein Expression in PIGT Mutants
| Protein | Patient Expression (% of Control) | Functional Impact |
|---|---|---|
| CD16 | 16.92% | Impaired NK cell immunity |
| CD24 | 22.16% | Reduced cell signaling |
| CD59 | 96.22% | Normal complement regulation |
Data derived from flow cytometry .
Therapeutic and Diagnostic Implications
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Biomarker Potential: CD16 reduction is a hallmark of PIGT dysfunction, aiding in pathogenicity assessment .
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Experimental Therapies: Histone deacetylase inhibitors (e.g., butyrate) show promise in upregulating GPI biosynthesis in PIGM mutants, suggesting analogous strategies for PIGT .
Future Directions
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High-Throughput Screening: Develop antibodies for novel GPI-anchored biomarkers.
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Gene Therapy: Explore CRISPR/Cas9 editing to correct PIGT mutations.
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Clinical Trials: Evaluate GPI-stabilizing drugs in PNH and MCAHS3 patients.
Product Specs
Constituents: 50% Glycerol, 0.01M PBS, pH 7.4
Target Background
- Whole-exome sequencing revealed compound heterozygous mutations (c.250G > T, p.Glu84X and c.1096G > T, p.Gly366Trp) in PIGT (NM_015937.5). These mutations were confirmed using Sanger sequencing, leading to the diagnosis of inherited GPI anchor deficiency associated with PIGT gene mutations. PMID: 28728837
- Studies using PIGT-knockout HEK293 cells demonstrated that the p.(E237Q) mutation results in a slight decrease in the amount of CD59 anchored to the cell membrane. PMID: 28327575
- Mutations in PIGT have been identified as the underlying cause of a novel autosomal recessive intellectual disability syndrome. PMID: 23636107
- Both germline and somatic mutations in PIGT have been linked to paroxysmal nocturnal hemoglobinuria. PMID: 23733340
- PIGT is localized to the endoplasmic reticulum (ER) due to its transmembrane span. PMID: 15713669
