Preclinical testing of new therapeutic approaches in a mouse model of congenital erythrocytosis with mutated erythropoietin receptor

Název projektu anglicky
Preclinical testing of new therapeutic approaches in a mouse model of congenital erythrocytosis with mutated erythropoietin receptor
Anotace anglicky
Primary familial and congenital polycythemia (PFCP) is an ultra-rare congenital red blood cell (RBC) disorder characterized by increased red cell mass. We previously developed a mouse model expressing a mutant human erythropoietin receptor (mtHEPOR), which closely mimics the human disease. Our findings revealed developmentally specific alterations in erythropoiesis in mtHEPOR mice, associated with changes in iron homeostasis and reduced RBC survival. This study aims to explore potential therapies targeting iron metabolism and erythrophagocytosis to mitigate erythrocytosis in PFCP. Specifically, we will test hepcidin agonist to modulate the hepcidin-ferroportin axis and anti-CD47 treatment to block the CD47-SIRPα interaction, preventing erythrophagocytosis. Additionally, we will examine dietary iron modulation to compare the effects of absolute versus functional iron deficiency. We will investigate CD47 downregulation in mtHEPOR mice and perform metabolomic analysis of RBCs. These approaches will enhance our understanding of both pathological and physiological erythropoiesis.

Kategorie VaV
ZV - Základní výzkum
OECD FORD - hlavní obor
30205 - Hematology
OECD FORD - vedlejší obor
30105 - Physiology (including cytology)
OECD FORD - další vedlejší obor
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CEP - odpovídající obory <br>(dle <a href="http://www.vyzkum.cz/storage/att/E6EF7938F0E854BAE520AC119FB22E8D/Prevodnik_oboru_Frascati.pdf">převodníku</a>)
ED - Fyziologie<br>FD - Onkologie a hematologie

Důvěrnost údajů
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Systémové označení dodávky dat
CEP26-GA0-GA-R
Datum dodání záznamu
4. 5. 2026

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