Deletion of TLR2 + erythro‐myeloid progenitors leads to embryonic lethality in mice
Autor: | Dominik Filipp, Jana Balounova, Tomáš Brabec, Matouš Vobořil, Iva Splichalova, Radislav Sedlacek |
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Rok vydání: | 2021 |
Předmět: |
0301 basic medicine
Myeloid Transgene Immunology Embryogenesis Embryo Biology Embryonic stem cell Cell biology 03 medical and health sciences Haematopoiesis 030104 developmental biology 0302 clinical medicine medicine.anatomical_structure Gene knockin medicine Immunology and Allergy Yolk sac 030215 immunology |
Zdroj: | European Journal of Immunology. 51:2237-2250 |
ISSN: | 1521-4141 0014-2980 |
Popis: | Early embryonic hematopoiesis in mammals is defined by three successive waves of hematopoietic progenitors which exhibit a distinct hematopoietic potential and provide continuous support for the development of the embryo and adult organism. Although the functional importance of each of these waves has been analyzed, their spatio-temporal overlap and the lack of wave-specific markers hinders the accurate separation and assessment of their functional roles during early embryogenesis. We have recently shown that TLR2, in combination with c-kit, represents the earliest signature of emerging precursors of the second hematopoietic wave, erythro-myeloid precursors (EMPs). Since the onset of Tlr2 expression distinguishes EMPs from primitive progenitors which coexist in the yolk sac from E7.5, we generated a novel transgenic "knock in" mouse model, Tlr2Dtr ,suitable for inducible targeted depletion of TLR2+ EMPs. In this model, the red fluorescent protein and diphtheria toxin receptor sequences are linked via a P2A sequence and inserted into the Tlr2 locus before its stop codon. We show that a timely-controlled deletion of TLR2+ EMPs in Tlr2Dtr embryos results in a marked decrease in both erythroid as well as myeloid lineages and, consequently, in embryonic lethality peaking before E13.5. These findings validate the importance of EMPs in embryonic development. This article is protected by copyright. All rights reserved. |
Databáze: | OpenAIRE |
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