Excessive erythrocytosis in adult mice overexpressing erythropoietin leads to hepatic, renal, neuronal, and muscular degeneration

Heinicke, Katja; Baum, Oliver; Ogunshola, Omolara O; Vogel, Johannes; Stallmach, Thomas; Wolfer, David P; Keller, Stephan; Weber, Klaus; Wagner, Peter D; Gassmann, Max; Djonov, Valentin (2006). Excessive erythrocytosis in adult mice overexpressing erythropoietin leads to hepatic, renal, neuronal, and muscular degeneration. American journal of physiology - regulatory, integrative and comparative physiology, 291(4), R947-56. Bethesda, Md.: American Physiological Society 10.1152/ajpregu.00152.2006

Full text not available from this repository. (Request a copy)

To investigate the consequences of inborn excessive erythrocytosis, we made use of our transgenic mouse line (tg6) that constitutively overexpresses erythropoietin (Epo) in a hypoxia-independent manner, thereby reaching hematocrit levels of up to 0.89. We detected expression of human Epo in the brain and, to a lesser extent, in the lung but not in the heart, kidney, or liver of tg6 mice. Although no acute cardiovascular complications are observed, tg6 animals have a reduced lifespan. Decreased swim performance was observed in 5-mo-old tg6 mice. At about 7 mo, several tg6 animals developed spastic contractions of the hindlimbs followed by paralysis. Morphological analysis by light and electron microscopy showed degenerative processes in liver and kidney characterized by increased vascular permeability, chronic progressive inflammation, hemosiderin deposition, and general vasodilatation. Moreover, most of the animals showed severe nerve fiber degeneration of the sciatic nerve, decreased number of neuromuscular junctions, and degeneration of skeletal muscle fibers. Most probably, the developing demyelinating neuropathy resulted in muscular degeneration demonstrated in the extensor digitorum longus muscle. Taken together, chronically increased Epo levels inducing excessive erythrocytosis leads to multiple organ degeneration and reduced life expectancy. This model allows investigation of the impact of excessive erythrocytosis in individuals suffering from polycythemia vera, chronic mountain sickness, or in subjects tempted to abuse Epo by means of gene doping.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Pre-clinic Human Medicine > Institute of Anatomy > Functional Anatomy
04 Faculty of Medicine > Pre-clinic Human Medicine > Institute of Anatomy

UniBE Contributor:

Baum, Oliver and Djonov, Valentin

ISSN:

0363-6119

ISBN:

16690772

Publisher:

American Physiological Society

Language:

English

Submitter:

Factscience Import

Date Deposited:

04 Oct 2013 14:46

Last Modified:

04 May 2014 23:13

Publisher DOI:

10.1152/ajpregu.00152.2006

PubMed ID:

16690772

Web of Science ID:

000240457600011

URI:

https://boris.unibe.ch/id/eprint/18925 (FactScience: 1196)

Actions (login required)

Edit item Edit item
Provide Feedback