TY  - JOUR
AU  - Waldmann, Rebekka
AU  - Werner, Franziska
AU  - Tasdogan, Alpaslan
AU  - Maier, Felix Immanuel
AU  - Kohlhofer, Ursula
AU  - Gonzalez-Menendez, Irene
AU  - de Fend, Leticia Quintanilla
AU  - Puarr, Amrit Kaur
AU  - Arkell, Ruth Maree
AU  - Enders, Anselm
AU  - Hoenig, Manfred
AU  - Schrezenmeier, Hubert
AU  - Fehling, Hans Joerg
AU  - Schwarz, Klaus
AU  - Pannicke, Ulrich
TI  - AK2-Deficient Mice Recapitulate Impaired Lymphopoiesis of Reticular Dysgenesis Patients, but Also Lack Erythropoiesis.
JO  - European journal of immunology
VL  - 55
IS  - 7
SN  - 0014-2980
CY  - Weinheim
PB  - Wiley-VCH
M1  - DKFZ-2025-01391
SP  - e51466
PY  - 2025
AB  - 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.
KW  - Animals
KW  - Mice, Knockout
KW  - Mice
KW  - Erythropoiesis: genetics
KW  - Erythropoiesis: immunology
KW  - Lymphopoiesis: genetics
KW  - Humans
KW  - Adenylate Kinase: genetics
KW  - Adenylate Kinase: deficiency
KW  - Adenylate Kinase: metabolism
KW  - Disease Models, Animal
KW  - Severe Combined Immunodeficiency: genetics
KW  - Thymus Gland: pathology
KW  - Leukopenia
KW  - AK2‐deficient mouse model (Other)
KW  - impaired lymphopoiesis (Other)
KW  - reticular dysgenesis (Other)
KW  - severe anaemia (Other)
KW  - adenylate kinase 2 (NLM Chemicals)
KW  - Adenylate Kinase (NLM Chemicals)
LB  - PUB:(DE-HGF)16
C6  - pmid:40654267
C2  - pmc:PMC12257577
DO  - DOI:10.1002/eji.202451466
UR  - https://inrepo02.dkfz.de/record/302851
ER  -