scholarly journals Expression of the Wilson disease gene is deficient in the Long-Evans Cinnamon rat

1994 ◽  
Vol 301 (1) ◽  
pp. 1-4 ◽  
Author(s):  
Y Yamaguchi ◽  
M E Heiny ◽  
N Shimizu ◽  
T Aoki ◽  
J D Gitlin
Keyword(s):  
Wilson Disease ◽  
Molecular Basis ◽  
Disease Gene ◽  
Genetic Disorder ◽  
Copper Accumulation ◽  
Hepatic Copper ◽  
Examine Gene Expression ◽  
Bona Fide ◽  
Rat Strain ◽  
Long Evans

Long-Evans Cinnamon rats develop a necrotizing hepatitis characterized by excessive hepatic copper accumulation, defective holoceruloplasmin biosynthesis and impaired biliary copper excretion. To elucidate the molecular basis of this defect, a cDNA clone encoding the rat Wilson disease gene was isolated and used to examine gene expression in selected tissues from normal and Long-Evans Cinnamon rats. Although this cDNA readily detects Wilson transcripts in liver and other tissues from normal rats, such transcripts are entirely absent from tissues derived from the Long-Evans Cinnamon rat strain. These data therefore identify the Long-Evans Cinnamon rat as the first bona fide animal model of Wilson disease and suggest that this rat strain may be a valuable resource in the study of this genetic disorder.

Hepatic Copper Accumulation Induces DNA Strand Breaks in the Liver Cells of Long-Evans Cinnamon Strain Rats

2000 ◽  
Vol 276 (1) ◽  
pp. 174-178 ◽  
Author(s):  
Masanobu Hayashi ◽  
Tomoko Kuge ◽  
Daiji Endoh ◽  
Kenji Nakayama ◽  
Jiro Arikawa ◽  
...  
Keyword(s):  
Dna Strand Breaks ◽  
Liver Cells ◽  
Copper Accumulation ◽  
Strand Breaks ◽  
Hepatic Copper ◽  
Long Evans ◽  
Dna Strand

Transient Elastography to Represent Hepatic Copper Accumulation in Wilson Disease

2020 ◽  
Vol 57 (8) ◽  
pp. 762-763
Author(s):  
Jirakorn Jamrasnaradom ◽  
Palittiya Sintusek
Keyword(s):  
Wilson Disease ◽  
Transient Elastography ◽  
Copper Accumulation ◽  
Hepatic Copper

scholarly journals Consequences of Copper Accumulation in the Livers of the Atp7b−/− (Wilson Disease Gene) Knockout Mice

2006 ◽  
Vol 168 (2) ◽  
pp. 423-434 ◽  
Author(s):  
Dominik Huster ◽  
Milton J. Finegold ◽  
Clinton T. Morgan ◽  
Jason L. Burkhead ◽  
Randal Nixon ◽  
...  
Keyword(s):  
Knockout Mice ◽  
Wilson Disease ◽  
Disease Gene ◽  
Gene Knockout ◽  
Copper Accumulation ◽  
Gene Knockout Mice

Metabolic Liver Diseases: Wilson Disease and alpha 1-Antitrypsin Deficiency

2015 ◽  
Author(s):  
Uri Avissar
Keyword(s):  
Wilson Disease ◽  
Metabolic Diseases ◽  
Clinical Presentation ◽  
Genetic Disorder ◽  
Neuropsychiatric Symptoms ◽  
Periodic Acid ◽  
Copper Accumulation ◽  
Suggested Approach ◽  
Monitoring Therapy ◽  
Antitrypsin Deficiency

Two significant metabolic diseases of the liver are Wilson disease (WD) and α1-antitrypsin deficiency (AATD). WD is defined as an autosomal recessive disorder caused by mutations in the ATP7B gene of copper metabolism, leading to copper accumulation in multiple organs, notably the liver and brain, with ensuing injury giving way to hepatic and neuropsychiatric symptoms. AATD is also a genetic disorder but is distinguished by the production of a defective protease inhibitor, which leads to hepatic and pulmonary injury. This review of WD and AATD addresses their respective epidemiologies, genetics, pathophysiologies, diagnoses, differential diagnoses, managements, complications, and prognoses. Figures show the pathophysiology, clinical presentation, and liver histology of WD; suggested approaches to the diagnosis of WD, suspected WD, and family screening of first-degree relatives of WD patients; monitoring therapy in WD disease; schematic representation of the α1-antitrypsin (AAT) mechanism of action and polymerization of the Z mutation variant; pathophysiology and clinical presentation of AATD; periodic acid–Schiff–positive diastase-resistant globules in AATD; and suggested approach to AAT diagnosis and management. Tables list the causes of low ceruloplasmin, medications used in WD, and AAT variants and risk of disease. This review contains 12 highly rendered figures, 3 tables, and 167 references.

scholarly journals Investigation of Genetic Modifiers of Copper Toxicosis in Labrador Retrievers

Life ◽  
2020 ◽  
Vol 10 (11) ◽  
pp. 266
Author(s):  
Xiaoyan Wu ◽  
Elise R. den Boer ◽  
Manon Vos-Loohuis ◽  
Frank G. van Steenbeek ◽  
Glen R. Monroe ◽  
...  
Keyword(s):  
Genetic Disorder ◽  
Copper Accumulation ◽  
Genetic Modifiers ◽  
Replication Cohort ◽  
Reference Allele ◽  
Alcoholic Fatty Liver ◽  
Copper Toxicosis ◽  
Hepatic Copper ◽  
Targeted Next Generation Sequencing ◽  
Labrador Retrievers

Copper toxicosis is a complex genetic disorder in Labrador retrievers characterized by hepatic copper accumulation eventually leading to liver cirrhosis. The variation of hepatic copper levels in Labrador retrievers has been partly explained by mutations in ATP7A c.980C>T and ATP7B c.4358G>A. To further elucidate the genetic background of this disease, we used targeted Next Generation Sequencing (NGS) in a cohort of 95 Labrador retrievers to analyze 72 potential modifier genes for variations associated with hepatic copper levels. Variants associated with copper levels were subsequently evaluated in a replication cohort of 144 Labrador retrievers. A total of 44 variants in 25 different genes were identified, of which four showed significant association with copper levels. Of the four variants found associated with hepatic copper levels in the NGS cohort, one was validated in the replication cohort. The non-reference allele of the variant NC_006602.3.g.52434480C>T in RETN resulting in amino-acid change p.Leu7Phe was associated with decreased hepatic copper levels. In humans, resistin is associated with severity of non-alcoholic fatty liver disease, fibrosis, cirrhosis and mitochondrial dysfunction in hepatocytes. Further studies are needed to investigate the biological function of RETN p.Leu7Phe in the development of copper toxicosis in Labrador retrievers.

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