Related Experiment Video
Updated: May 2, 2026
09:37
Navigating MARRVEL, a Web-Based Tool that Integrates Human Genomics and Model Organism Genetics Information
Published on: August 15, 2019
8.9K
Mutations in TJP2 cause progressive cholestatic liver disease
Melissa Sambrotta1, Sandra Strautnieks2, Efterpi Papouli3
1Institute of Liver Studies, Division of Transplantation Immunology and Mucosal Biology, King's College London School of Medicine, London, UK.
Nature Genetics
|March 12, 2014
Summary
Protein-truncating mutations in the tight junction protein 2 gene (TJP2) cause severe liver disease. This disrupts liver tight junctions, unlike in mouse models, revealing species-specific genetic disease mechanisms.
Area of Science:
- Hepatology
- Genetics
- Molecular Biology
Background:
- Understanding cholestasis requires identifying its genetic underpinnings.
- The liver's physiology and pathophysiology are closely linked to genetic factors.
Purpose of the Study:
- To investigate the role of the tight junction protein 2 gene (TJP2) in cholestatic liver disease.
- To elucidate the molecular mechanisms by which TJP2 mutations lead to liver dysfunction.
Main Methods:
- Analysis of protein-truncating mutations in the TJP2 gene.
- Assessment of protein localization and tight-junction structure.
- Comparison of human disease findings with data from TJP2 knockout mouse models.
Main Results:
- Protein-truncating mutations in TJP2 lead to impaired protein localization.
- These mutations disrupt the structure of tight junctions in the liver.
- Severe cholestatic liver disease results from TJP2 mutations.
- Observed human pathology contrasts with the embryonic-lethal phenotype in knockout mice.
Conclusions:
- TJP2 is crucial for maintaining liver tight-junction integrity.
- Genetic defects in TJP2 cause severe cholestatic liver disease in humans.
- Species- and organ-specific differences in junctional complex redundancy influence disease presentation.
Related Concept Videos
01:21Chronic Pancreatitis II: Pathophysiology
30
Chronic pancreatitis is a progressive and irreversible inflammation of the pancreas, most often caused by long-term alcohol abuse, but it can also be related to ductal obstruction, smoking, or genetic factors.Chronic pancreatitis occurs when the pancreas is repeatedly exposed to harmful agents like alcohol, smoking, ductal obstruction, or genetic predisposition. These factors lead to the release of toxic metabolites and inflammatory cytokines, sustaining chronic inflammation in the pancreatic...
30
01:27Pharmacogenetics of Phase II Enzymes: N-acetyltransferase, Thiopurine S-methyltransferase, UDP-glucuronosyltransferase
94
Phase II biotransformation reactions are essential for detoxifying and eliminating xenobiotics, including many pharmaceutical compounds. These reactions typically involve conjugation, the covalent attachment of polar endogenous groups such as glucuronic acid, sulfate, methyl, or acetyl moieties to functional groups introduced during Phase I metabolism. The resulting conjugates are more water-soluble, enabling efficient renal or biliary excretion.The major classes of Phase II enzymes include...
94
01:21Acute Pancreatitis II: Pathophysiology
46
The pathophysiology of acute pancreatitis centers on injury to pancreatic acinar cells, which initiates a cascade of harmful intracellular events.This injury leads to premature activation of trypsinogen to trypsin in the pancreas. Trypsin then activates other digestive enzymes, such as chymotrypsin, elastase, and phospholipase A2, which begin breaking down pancreatic tissue. The resulting autodigestion causes local inflammation, tissue swelling, hemorrhage, and fat necrosis.Injured acinar cells...
46
01:22Effect of Hepatic Disease on Pharmacokinetics: Pathophysiologic Assessment and Liver Function Test
271
In clinical practice, the direct measurement of hepatic blood flow to evaluate liver function presents significant challenges due to the intricate and specialized nature of the necessary techniques. Consequently, healthcare professionals often rely on empirical estimates derived from thorough patient examinations and liver function tests to gauge liver health. Among the tools at their disposal, the Child–Pugh and MELD scoring systems stand out for their ability to categorize and assess...
271
01:29Hepatic Encephalopathy
53
DefinitionHepatic encephalopathy is a reversible neurologic syndrome that results from advanced liver dysfunction or portosystemic shunting. It leads to disturbances in cognition, behavior, and motor function due to the brain’s exposure to gut-derived toxins that the liver fails to detoxify.EtiologyThis condition develops either in the setting of acute fulminant hepatitis or progressively during chronic liver disease, such as cirrhosis and portal hypertension. Portosystemic...
53
01:31Translation
16.8K
Translation is the process of synthesizing proteins from the genetic information carried by messenger RNA (mRNA). Following transcription, it constitutes the final step in the expression of genes. This process is carried out by ribosomes, complexes of protein and specialized RNA molecules. Ribosomes, transfer RNA (tRNA), and other proteins produce a chain of amino acids—the polypeptide—as the end product of translation.
Translation Produces the Building Blocks of Life
Proteins are...
Translation Produces the Building Blocks of Life
Proteins are...
16.8K