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| IJCEP Copyright © 2007-All rights reserved. |
| International Journal of Clinical and Experimental Pathology |
Int J Clin Exp Pathol 2(1), 34-47; 2008
Original Article
Decreased survival and hepato-renal pathology in mice with C-terminally truncated
GP73 (GOLPH2)
Lorinda Marie Wright, Sheri Yong, Maria Mrozowicz Picken, Don Rockey, Claus Jürgen Fimmel
Division of Gastroenterology, Hepatology and Nutrition, Loyola University, Stritch School of Medicine, Maywood, IL, USA, Edward Hines VA
Medical Center, Hines, IL, USA, Department of Pathology, Loyola University, Stritch School of Medicine, Maywood, IL, USA, and Internal
Medicine, Digestive & Liver Diseases, UT Southwestern Medical Center, Dallas, TX, USA
Received 21 March 2008; Accepted with revision 14 April 2008; Available online 24 April 2008
Abstract: GP73 (Golph2) is a type II Golgi-localized integral membrane protein that is normally expressed in epithelial cells of many
human tissues, and that is highly upregulated in liver disease. While its function is unknown, the GP73 C-terminus contains putative
protein-interaction domains. We used a gene trap approach to generate mice with a severe truncation of the GP73 C-terminus (GP73tr/tr)
in order to investigate the physiological role of this protein. GP73tr/tr mice were born at the expected rate and were fertile, but cumulative
survival was significantly reduced compared to wild-type controls, particularly in females. GP73tr/tr mice developed varying degrees of
renal disease, most notably focal segmental glomerulosclerosis and hyaline thrombi. In addition to renal abnormalities, GP73tr/tr mice
developed marked microvesicular hepatic steatosis, hepatocyte nuclear membrane irregularities and intranuclear inclusions. GP73tr/tr
expression in morphologically normal kidneys and livers was constitutively low, but was strikingly upregulated in the diseased kidney
cortex, and was upregulated in livers in animals of advanced age. Despite the substantial morphological changes in the kidneys and liver,
routine screening serum assays provided no evidence of renal or hepatic dysfunction. Consequently, the cause of the increased mortality
of GP73tr/tr animals is unclear at present. Our study indicates that GP73 is essential for normal survival, and suggests multiple roles for
GP73 in epithelial cell function in the kidney and liver. (IJCEP803012).
Key Words: GP73 (Golph2), epithelial cells, Golgi membrane protein, hyaline thrombi, glomerulosclerosis, hepatic steatosis
Full text PDF
Address all correspondences to: Lorinda M. Wright, Ph.D., Division of Gastroenterology, Hepatology and Nutrition, Loyola University,
Stritch School of Medicine, 2160 South 1st Avenue, Maywood, IL 60153, USA, Tel.: 708 202-5717, Fax: 708 216-4113, E-mail:
LMWright@LUMC.edu
Original Article
Decreased survival and hepato-renal pathology in mice with C-terminally truncated
GP73 (GOLPH2)
Lorinda Marie Wright, Sheri Yong, Maria Mrozowicz Picken, Don Rockey, Claus Jürgen Fimmel
Division of Gastroenterology, Hepatology and Nutrition, Loyola University, Stritch School of Medicine, Maywood, IL, USA, Edward Hines VA
Medical Center, Hines, IL, USA, Department of Pathology, Loyola University, Stritch School of Medicine, Maywood, IL, USA, and Internal
Medicine, Digestive & Liver Diseases, UT Southwestern Medical Center, Dallas, TX, USA
Received 21 March 2008; Accepted with revision 14 April 2008; Available online 24 April 2008
Abstract: GP73 (Golph2) is a type II Golgi-localized integral membrane protein that is normally expressed in epithelial cells of many
human tissues, and that is highly upregulated in liver disease. While its function is unknown, the GP73 C-terminus contains putative
protein-interaction domains. We used a gene trap approach to generate mice with a severe truncation of the GP73 C-terminus (GP73tr/tr)
in order to investigate the physiological role of this protein. GP73tr/tr mice were born at the expected rate and were fertile, but cumulative
survival was significantly reduced compared to wild-type controls, particularly in females. GP73tr/tr mice developed varying degrees of
renal disease, most notably focal segmental glomerulosclerosis and hyaline thrombi. In addition to renal abnormalities, GP73tr/tr mice
developed marked microvesicular hepatic steatosis, hepatocyte nuclear membrane irregularities and intranuclear inclusions. GP73tr/tr
expression in morphologically normal kidneys and livers was constitutively low, but was strikingly upregulated in the diseased kidney
cortex, and was upregulated in livers in animals of advanced age. Despite the substantial morphological changes in the kidneys and liver,
routine screening serum assays provided no evidence of renal or hepatic dysfunction. Consequently, the cause of the increased mortality
of GP73tr/tr animals is unclear at present. Our study indicates that GP73 is essential for normal survival, and suggests multiple roles for
GP73 in epithelial cell function in the kidney and liver. (IJCEP803012).
Key Words: GP73 (Golph2), epithelial cells, Golgi membrane protein, hyaline thrombi, glomerulosclerosis, hepatic steatosis
Full text PDF
Address all correspondences to: Lorinda M. Wright, Ph.D., Division of Gastroenterology, Hepatology and Nutrition, Loyola University,
Stritch School of Medicine, 2160 South 1st Avenue, Maywood, IL 60153, USA, Tel.: 708 202-5717, Fax: 708 216-4113, E-mail:
LMWright@LUMC.edu