Disruption of the mouse Shmt2 gene confers embryonic anaemia via foetal liver-specific metabolomic disorders

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Tani , H , Mito , T , Velagapudi , V , Ishikawa , K , Umehara , M , Nakada , K , Suomalainen , A & Hayashi , J-I 2019 , ' Disruption of the mouse Shmt2 gene confers embryonic anaemia via foetal liver-specific metabolomic disorders ' , Scientific Reports , vol. 9 , 16054 . https://doi.org/10.1038/s41598-019-52372-6

Title: Disruption of the mouse Shmt2 gene confers embryonic anaemia via foetal liver-specific metabolomic disorders
Author: Tani, Haruna; Mito, Takayuki; Velagapudi, Vidya; Ishikawa, Kaori; Umehara, Moe; Nakada, Kazuto; Suomalainen, Anu; Hayashi, Jun-Ichi
Contributor: University of Helsinki, Research Programs Unit
University of Helsinki, University Management
University of Helsinki, HUSLAB
Date: 2019-11-05
Language: eng
Number of pages: 11
Belongs to series: Scientific Reports
ISSN: 2045-2322
URI: http://hdl.handle.net/10138/307170
Abstract: In a previous study, we proposed that age-related mitochondrial respiration defects observed in elderly subjects are partially due to age-associated downregulation of nuclear-encoded genes, including serine hydroxymethyltransferase 2 (SHMT2), which is involved in mitochondrial one-carbon (1C) metabolism. This assertion is supported by evidence that the disruption of mouse Shmt2 induces mitochondrial respiration defects in mouse embryonic fibroblasts generated from Shmt2-knockout E13.5 embryos experiencing anaemia and lethality. Here, we elucidated the potential mechanisms by which the disruption of this gene induces mitochondrial respiration defects and embryonic anaemia using Shmt2-knockout E13.5 embryos. The livers but not the brains of Shmt2-knockout E13.5 embryos presented mitochondrial respiration defects and growth retardation. Metabolomic profiling revealed that Shmt2 deficiency induced foetal liver-specific downregulation of 1C-metabolic pathways that create taurine and nucleotides required for mitochondrial respiratory function and cell division, respectively, resulting in the manifestation of mitochondrial respiration defects and growth retardation. Given that foetal livers function to produce erythroblasts in mouse embryos, growth retardation in foetal livers directly induced depletion of erythroblasts. By contrast, mitochondrial respiration defects in foetal livers also induced depletion of erythroblasts as a consequence of the inhibition of erythroblast differentiation, resulting in the manifestation of anaemia in Shmt2-knockout E13.5 embryos.
Subject: MITOCHONDRIAL-DNA MUTATIONS
NEURAL-TUBE DEFECTS
MICE
NUCLEAR
METABOANALYST
DYSFUNCTION
DEFICIENCY
PHENOTYPES
DELETION
DISEASES
3111 Biomedicine
1184 Genetics, developmental biology, physiology
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