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. Author manuscript; available in PMC: 2022 Jul 2.
Published in final edited form as: IUBMB Life. 2018 Jul 1;70(7):612–624. doi: 10.1002/iub.1870

Table 1. Transgenic mouse models with increased mitochondrial function with concomitant loss of stemness in hematopoietic system.

Phenotype
Model Lethality In vitro In vivo Reference
Mx-Cre+;FoxO1/3/4l/l
  • Defective HSC and CLP colony forming activity

  • Expansion of myeloid lineage and decrease in lymphoid commitment

  • Loss of stem cell population in bone marrow

  • Increased ROS levels in HSCs

47
FoxO3a–/–
  • Mild reduction in HSC clonogenic capacity

  • Deteriorated resistance to myelotoxic stress

  • Increased HSC cycling

46
Atm–/– By 24 weeks, post BM failure
  • Increase in intracellular H2O2 in LSK

  • Increased ROS accumulation

  • BM failure as early as 24 weeks

43
Mx1-Cre-;Pdk2,4–/–
  • Decrease in the number of LSK cells in vitro

  • Reduction in LT-HSC fraction in vitro

  • Loss of quiescence in HSCs and steady state hematopoiesis affected

  • Accumulated mitochondrial ROS and diminished repopulation capacity

  • Multilineage engraftment capacity remained unaffected

5
Mx-1-Cre;Tscfl/fl
  • Increase in the size and number of erythroid, macrophage, megakaryocyte and granulocyte colonies

  • Increase in percentage of apoptotic cells in the aforesaid colonies

  • Increased mitochondrial biogenesis, increased mitochondrial DNA expression, increased ROS

  • Active cycling of HSCs and loss of transplantation potential

  • Premature aging of the hematopoietic system

52
Sirt7–/– Not mentioned
  • Increased mitochondrial mass and ATP levels in HSC, increased mitochondrial function

  • Loss of hematopoietic function

50
Vav1-Cre;Mtch2fl/fl
  • Decreased CFU-C potential in HSCs

  • CFU-Cs from cKO mice less sensitive to radiation damage

  • Increased mitochondrial pathways in HSCs, increase in size and activity of mitochondria

  • Increased HSC entry into cell cycle, decreased frequency of primitive HSCs

6
Mx1-Cre;HIF1afl/fl
  • Reduced HSC frequency and number with age

4
Germline Rev1–/– Lifespan shorter than WT littermates
  • Rev1 HSC clonogenicity reduced

  • Loss of engraftment potential of HSCs

  • Functional loss of HSCs starting as early as E14 FL

79
Rev1–/– Xpc–/– ≈3.5 months
  • Embryos born in sub-Mendelian ratios

  • Smaller embryos than WT or single deficient littermates

  • Major hematopoietic defects; very less HSC numbers starting as early as E14 FL

  • Increased HSC cycling

79