Abstract
The most recent elucidation of an inherited disorder of the pancreas concerns the Johanson-Blizzard syndrome (JBS). Positional cloning identified loss-of-function mutations in the UBRI gene on the long arm of chromosome 15 to be the cause of JBS in more than a dozen patients. In patients with JBS the absence of UBRI results in early prenatal destruction of the exocrine pancreas that involves impaired apoptosis, induced necrosis, and prominent inflammation. Knockout mice with absent UBR1 expression suffer from exocrine pancreatic insufficiency and increased susceptibility to experimental pancreatitis. The UBR1 protein substrate, presumably impaired degradation of which causes JBS, is not yet known.
Publication types
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Research Support, Non-U.S. Gov't
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Review
MeSH terms
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Abnormalities, Multiple / enzymology
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Abnormalities, Multiple / genetics*
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Abnormalities, Multiple / physiopathology
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Animals
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Apoptosis / genetics
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Apoptosis / physiology
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Exocrine Pancreatic Insufficiency / enzymology
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Exocrine Pancreatic Insufficiency / genetics*
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Exocrine Pancreatic Insufficiency / physiopathology
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Female
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Hearing Disorders / enzymology
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Hearing Disorders / genetics
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Hearing Disorders / physiopathology
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Humans
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Intellectual Disability / enzymology
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Intellectual Disability / genetics
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Intellectual Disability / physiopathology
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Mice
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Mice, Knockout
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Mutation, Missense / genetics
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Mutation, Missense / physiology
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Ubiquitin-Protein Ligases / genetics*
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Ubiquitin-Protein Ligases / metabolism
Substances
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UBR1 protein, human
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Ubiquitin-Protein Ligases