Zenker Martin, Mayerle Julia, Reis André, Lerch Markus M
Institute of Human Genetics, University of Erlangen-Nuremberg, Schwabachanlage 10, 91054 Erlangen, Germany.
Endocrinol Metab Clin North Am. 2006 Jun;35(2):243-53, vii-viii. doi: 10.1016/j.ecl.2006.02.013.
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.
最近对一种遗传性胰腺疾病的阐明涉及约翰森-布利扎德综合征（JBS）。定位克隆发现，15号染色体长臂上的UBR1基因功能丧失突变是十几名患者患JBS的原因。在JBS患者中，UBR1的缺失导致产前外分泌胰腺早期破坏，这涉及凋亡受损、诱导性坏死和显著炎症。缺乏UBR1表达的基因敲除小鼠患有外分泌胰腺功能不全，对实验性胰腺炎的易感性增加。UBR1蛋白底物尚不清楚，推测其降解受损导致了JBS。
