Delayed hemoglobin switching and perinatal neocytolysis in mice with gain-of-function erythropoietin receptor

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61989592%3A15110%2F16%3A33160517" target="_blank" >RIV/61989592:15110/16:33160517 - isvavai.cz</a>

Alternative codes found

RIV/00023736:_____/16:00011496

Result on the web

<a href="http://link.springer.com/article/10.1007%2Fs00109-015-1375-y" target="_blank" >http://link.springer.com/article/10.1007%2Fs00109-015-1375-y</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1007/s00109-015-1375-y" target="_blank" >10.1007/s00109-015-1375-y</a>

Result language

angličtina

Original language name

Delayed hemoglobin switching and perinatal neocytolysis in mice with gain-of-function erythropoietin receptor

Original language description

Mutations of the truncated cytoplasmic domain of human erythropoietin receptor (EPOR) result in gain-of-function of erythropoietin (EPO) signaling and a dominantly inherited polycythemia, primary familial and congenital polycythemia (PFCP). We interrogated the unexplained transient absence of perinatal polycythemia observed in PFCP patients using an animal model of PFCP to examine its erythropoiesis during embryonic, perinatal, and early postnatal periods. In this model, we replaced the murine EpoR gene (mEpoR) with the wild-type human EPOR (wtHEPOR) or mutant human EPOR gene (mtHEPOR) and previously reported that the gain-of-function mtHEPOR mice become polycythemic at 3~6 weeks of age, but not at birth, similar to the phenotype of PFCP patients. In contrast, wtHEPOR mice had sustained anemia. We report that the mtHEPOR fetuses are polycythemic, but their polycythemia is abrogated in the perinatal period and reappears again at 3 weeks after birth. mtHEPOR fetuses have a delayed switch from primitive to definitive erythropoiesis, augmented erythropoietin signaling, and prolonged Stat5 phosphorylation while the wtHEPOR fetuses are anemic. Our study demonstrates the in vivo effect of excessive EPO/EPOR signaling on developmental erythropoiesis switch and describes that fetal polycythemia in this PFCP model is followed by transient correction of polycythemia in perinatal life associated with low Epo levels and increased exposure of erythrocytes' phosphatidylserine. We suggest that neocytolysis contributes to the observed perinatal correction of polycythemia in mtHEPOR newborns as embryos leaving the hypoxic uterus are exposed to normoxia at birth.

Czech name

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Czech description

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Type

J_x - Unclassified - Peer-reviewed scientific article (Jimp, Jsc and Jost)

CEP classification

FD - Oncology and haematology

OECD FORD branch

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Project

Result was created during the realization of more than one project. More information in the Projects tab.

Continuities

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Publication year

2016

Confidentiality

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Name of the periodical

Journal of Molecular Medicine

ISSN

0946-2716

e-ISSN

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Volume of the periodical

94

Issue of the periodical within the volume

5

Country of publishing house

DE - GERMANY

Number of pages

12

Pages from-to

597-608

UT code for WoS article

000375715200011

EID of the result in the Scopus database

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