Quick Search:

uzh logo
Browse by:

Zurich Open Repository and Archive

Permanent URL to this publication: http://dx.doi.org/10.5167/uzh-2531

Föller, M; Feil, S; Ghoreschi, K; Koka, S; Gerling, A; Thunemann, M; Hofmann, F; Schuler, B; Vogel, J; Pichler, B; Kasinathan, R S; Nicolay, J P; Huber, S M; Lang, F; Feil, R (2008). Anemia and splenomegaly in cGKI-deficient mice. Proceedings of the National Academy of Sciences of the United States of America (PNAS), 105(18):6771-6776.

Accepted Version
View at publisher


To explore the functional significance of cGMP-dependent protein kinase type I (cGKI) in the regulation of erythrocyte survival, gene-targeted mice lacking cGKI were compared with their control littermates. By the age of 10 weeks, cGKI-deficient mice exhibited pronounced anemia and splenomegaly. Compared with control mice, the cGKI mutants had significantly lower red blood cell count, packed cell volume, and hemoglobin concentration. Anemia was associated with a higher reticulocyte number and an increase of plasma erythropoietin concentration. The spleens of cGKI mutant mice were massively enlarged and contained a higher fraction of Ter119(+) erythroid cells, whereas the relative proportion of leukocyte subpopulations was not changed. The Ter119(+) cGKI-deficient splenocytes showed a marked increase in annexin V binding, pointing to phosphatidylserine (PS) exposure at the outer membrane leaflet, a hallmark of suicidal erythrocyte death or eryptosis. Compared with control erythrocytes, cGKI-deficient erythrocytes exhibited in vitro a higher cytosolic Ca(2+) concentration, a known trigger of eryptosis, and showed increased PS exposure, which was paralleled by a faster clearance in vivo. Together, these results identify a role of cGKI as mediator of erythrocyte survival and extend the emerging concept that cGMP/cGKI signaling has an antiapoptotic/prosurvival function in a number of cell types in vivo.


98 citations in Web of Science®
97 citations in Scopus®
Google Scholar™



338 downloads since deposited on 06 Jun 2008
47 downloads since 12 months

Detailed statistics

Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:05 Vetsuisse Faculty > Institute of Veterinary Physiology
04 Faculty of Medicine > Center for Integrative Human Physiology
Dewey Decimal Classification:570 Life sciences; biology
610 Medicine & health
Date:May 2008
Deposited On:06 Jun 2008 11:52
Last Modified:05 Apr 2016 12:23
Publisher:National Academy of Sciences
Publisher DOI:10.1073/pnas.0708940105
PubMed ID:18443297

Users (please log in): suggest update or correction for this item

Repository Staff Only: item control page