PMID- 12829028
OWN - NLM
STAT- MEDLINE
DCOM- 20030807
LR  - 20220321
IS  - 0301-472X (Print)
IS  - 0301-472X (Linking)
VI  - 31
IP  - 6
DP  - 2003 Jun
TI  - Expansion of hematopoietic stem cell phenotype and activity in Trp53-null mice.
PG  - 521-7
AB  - OBJECTIVES: To study the effects of transformation-related protein 53 (Trp53) and 
      other genes on hematopoiesis and hematopoietic stem cells (HSCs). METHODS: 
      Frequencies of murine bone marrow cells (BMCs) with the 
      Lin(-)Sca-1(+)c-kit(+)CD34- phenotype were analyzed by flow cytometry, and were 
      increased in mice with germ-line deletion of the Trp53 (Trp53(-/-)) gene but not 
      in 25 other deletions of genes involved in cell cycling, development, cancer, or 
      hematopoiesis. Therefore, Trp53(-/-) and wild-type Trp53(+/+) mice were compared 
      using the following assays: complete blood counts, day-9 colony-forming unit 
      spleen (CFU-S), and competitive repopulation. In the latter assay, donor 
      repopulating ability was analyzed at one, three, and five months, while recipient 
      survival and recipient blood and bone marrow cell composition were analyzed at 
      five months, after transplantation. RESULTS: In comparison to wild-type controls, 
      Trp53(-/-) mice had normal blood and bone marrow cell counts, increased CD11b(+), 
      and decreased CD45R(+) cell proportions in blood and bone marrow, twice as many 
      Lin(-)Sca-1(+)c-kit(+)CD34(-) BMCs, and 37% more day-9 CFU-S. In the competitive 
      repopulation assay, Trp53(-/-) BMCs engrafted lethally irradiated recipients two 
      to four times better than Trp53(+/+) BMCs. The Trp53(-/-) engraftment advantage 
      increased with time in the recipients. Recipients of Trp53(-/-) donors had two to 
      three times more Lin(-)Sca-1(+)c-kit(+)CD34(-) BMCs than recipients of Trp53(+/+) 
      donors at five months after transplantation. However, only 44% of recipients of 
      Trp53(-/-) donors survived five months after trans-plantation, compared with 92% 
      of recipients of Trp53(+/+) donors. CONCLUSION: The Trp53-null allele expands 
      bone marrow Lin(-)Sca-1(+)c-kit(+)CD34(-) cells and the overall activity of HSCs; 
      however, it increases recipient mortality.
FAU - TeKippe, Michael
AU  - TeKippe M
AD  - The Jackson Laboratory, 600 Main Street, Bar Harbor, Maine 04609, USA.
FAU - Harrison, David E
AU  - Harrison DE
FAU - Chen, Jichun
AU  - Chen J
LA  - eng
PT  - Journal Article
PL  - Netherlands
TA  - Exp Hematol
JT  - Experimental hematology
JID - 0402313
RN  - 0 (CD11b Antigen)
RN  - 0 (Tumor Suppressor Protein p53)
RN  - EC 3.1.3.48 (Leukocyte Common Antigens)
SB  - IM
MH  - Animals
MH  - Bone Marrow Cells
MH  - Bone Marrow Transplantation
MH  - CD11b Antigen/analysis
MH  - Cell Count
MH  - Cell Division
MH  - Flow Cytometry
MH  - Graft Survival
MH  - Hematopoiesis
MH  - Hematopoietic Stem Cell Transplantation
MH  - Hematopoietic Stem Cells/*cytology
MH  - Immunophenotyping
MH  - Leukocyte Common Antigens/analysis
MH  - Mice
MH  - Mice, Knockout
MH  - Tumor Suppressor Protein p53/genetics/*physiology
EDAT- 2003/06/28 05:00
MHDA- 2003/08/09 05:00
CRDT- 2003/06/28 05:00
PHST- 2003/06/28 05:00 [pubmed]
PHST- 2003/08/09 05:00 [medline]
PHST- 2003/06/28 05:00 [entrez]
AID - S0301472X03000729 [pii]
AID - 10.1016/s0301-472x(03)00072-9 [doi]
PST - ppublish
SO  - Exp Hematol. 2003 Jun;31(6):521-7. doi: 10.1016/s0301-472x(03)00072-9.