[Establishment of a bone marrow failure mouse model by immune injury].
OBJECTIVE
To establish a mouse model for the study of pathophysiologic mechanism and treatment of bone marrow failure (BMF).


METHODS
Balb/c mice (recipient) were irradiated 5.0 Gy by gamma rays of (60)Co, and then infused 5 x 10(6) lymph node (LN) cells from DBA/2 mice (donor) in 4 hours. Pancytopenia was monitored by cell counting, bone marrow damage was assessed by histological staining and mononuclear cell counting. Serum IFN-gamma concentration was measured by ELISA. The proportion of Treg in spleen was detected by flow cytometry.


RESULTS
Irradiation and infusion of LN cells led to rapid development of severe pancytopenia and BM hypoplasia, which reached the most severity at d14. The pancytopenia remained at d28 and displayed no signs of recovery. The bone marrow was full of adipose cells with scarcity of hematopoietic cells at d14 and persisted at least for 28 days, being similar to the feature of aplastic anemia. Serum IFN-gamma concentration was 6.3 fold increased \[(170.0 +/- 17.0) vs (27.7 +/- 7.1) pg/ml\] at d6. Tregs were decreased after infusion, and then increased \[(3.38 +/- 0.52)%\] and recovered to normal \[(4.04 +/- 0.44)%\] at d21. The expression level of the specific transcription factor Foxp3 was similar to normal.


CONCLUSIONS
The MHC antigen of Balb/c mice is identical to that of DBA/2 mice, but their minor antigen differs. 5.0 Gy irradiation and then 5 x 10(6) lymphocyte infusion can induce BMF similar to the features of aplastic anemia.
Huang
Li-Fang
LF
Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
Zhou
Kun
K
Zhang
Na
N
Luo
Li
L
Zheng
Miao
M
Zhou
Sheng
S
Sun
Han-Ying
HY
Liu
Wen-Li
WL
D000741:Anemia, Aplastic / Q000209:etiology* / Q000276:immunology / Q000473:pathology; D000818:Animals; D001853:Bone Marrow / Q000473:pathology; D004195:Disease Models, Animal; D005260:Female; D005720:Gamma Rays / Q000009:adverse effects*; D007371:Interferon-gamma / Q000276:immunology; D017710:Lymphocyte Transfusion / Q000009:adverse effects*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D050378:T-Lymphocytes, Regulatory / Q000276:immunology
D007371:Interferon-gamma