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@ARTICLE{Waldmann:302851,
author = {R. Waldmann and F. Werner and A. Tasdogan$^*$ and F. I.
Maier and U. Kohlhofer and I. Gonzalez-Menendez and L. Q. de
Fend and A. K. Puarr and R. M. Arkell and A. Enders and M.
Hoenig and H. Schrezenmeier and H. J. Fehling and K. Schwarz
and U. Pannicke},
title = {{AK}2-{D}eficient {M}ice {R}ecapitulate {I}mpaired
{L}ymphopoiesis of {R}eticular {D}ysgenesis {P}atients, but
{A}lso {L}ack {E}rythropoiesis.},
journal = {European journal of immunology},
volume = {55},
number = {7},
issn = {0014-2980},
address = {Weinheim},
publisher = {Wiley-VCH},
reportid = {DKFZ-2025-01391},
pages = {e51466},
year = {2025},
abstract = {Reticular dysgenesis (RD) is a rare genetic disorder caused
by mutations in the adenylate kinase 2 (AK2) gene. It is
characterized by a T-B- severe combined immunodeficiency,
agranulocytosis, and sensorineural deafness. We established
and characterized a haematopoiesis-specific conditional
Ak2-knockout mouse model to provide a model system to study
the molecular pathophysiology of RD. As expected from the
human phenotype of RD, haematopoiesis-specific AK2-deficient
embryos had a small, atrophic thymus consisting mainly of
epithelial cells. No recognizable T-cell component was
observed, but B-cell lineage precursor cells were present in
the foetal liver. The effects of AK2 deficiency on
myelopoiesis were less severe in mice than in humans. The
absolute numbers of monocytes, macrophages, granulocytes and
megakaryocytes in foetal liver as well as colony-forming
precursors were not reduced. In contrast to humans,
haematopoiesis-specific Ak2-knockout mice exhibit embryonic
lethality between E13 and E15 due to severe anaemia caused
by an early block in definitive erythropoiesis. Murine
erythroid progenitors mainly express AK2 and only low levels
of functionally related kinases, which are unable to
compensate for AK2 deficiency, in contrast to human
erythroid progenitors.},
keywords = {Animals / Mice, Knockout / Mice / Erythropoiesis: genetics
/ Erythropoiesis: immunology / Lymphopoiesis: genetics /
Humans / Adenylate Kinase: genetics / Adenylate Kinase:
deficiency / Adenylate Kinase: metabolism / Disease Models,
Animal / Severe Combined Immunodeficiency: genetics / Thymus
Gland: pathology / Leukopenia / AK2‐deficient mouse model
(Other) / impaired lymphopoiesis (Other) / reticular
dysgenesis (Other) / severe anaemia (Other) / adenylate
kinase 2 (NLM Chemicals) / Adenylate Kinase (NLM Chemicals)},
cin = {ED01},
ddc = {610},
cid = {I:(DE-He78)ED01-20160331},
pnm = {899 - ohne Topic (POF4-899)},
pid = {G:(DE-HGF)POF4-899},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:40654267},
pmc = {pmc:PMC12257577},
doi = {10.1002/eji.202451466},
url = {https://inrepo02.dkfz.de/record/302851},
}