Hematopoiesis is severely altered in mice with an induced osteoblast deficiency
Hematopoiesis is severely altered in mice with an induced osteoblast deficiency
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DOI：
10.1182/blood-2003-11-4011
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发表时间：
2004-05-01
期刊：
影响因子：
20.3
通讯作者：
Aguila, HL
中科院分区：
文献类型：
--
作者：
Visnjic, D;Kalajzic, Z;Aguila, HL
我们以前报道了一个转基因小鼠模型表达疱疹病毒胸苷激酶（TK）基因的大鼠胶原α 1型启动子（Col2.3DeltaTK）的2.3-磷酸酶片段的控制下。该构建体赋予谱系特异性表达在发育中的成骨细胞中，允许在用更昔洛韦（GCV）处理后条件性消融成骨细胞谱系。在GCV治疗后，这些小鼠在骨形成上具有深刻的改变，导致进行性骨丢失。此外，给药动物也会丢失骨髓细胞。在这份报告中，我们的特点是造血参数GCV治疗的Col2.3DeltaTK小鼠，我们表明，治疗后，转基因动物失去淋巴，红细胞和骨髓祖细胞在骨髓中，其次是造血干细胞（HSC）的数量减少。与骨髓造血减少一起，在脾脏和肝脏中观察到活跃的髓外造血，如通过外周HSC和活跃的初级体外造血的增加所测量的。GCV停药后，成骨细胞重新出现在骨室中，髓内造血恢复，髓外造血减少。这些观察结果直接证明了成骨细胞在造血中的作用，并提供了一个模型，以研究骨髓间充质和造血隔室之间的相互作用。(C)2004年，美国血液学会。
We previously reported a transgenic mouse model expressing herpesvirus thymidine kinase (TK) gene under the control of a 2.3-kilobase fragment of the rat collagen alpha1 type I promoter (Col2.3DeltaTK). This construct confers lineage-specific expression in developing osteoblasts, allowing the conditional ablation of osteoblast lineage after treatment with ganciclovir (GCV). After GCV treatment these mice have profound alterations on bone formation leading to a progressive bone loss. In addition, treated animals also lose bone marrow cellularity. In this report we characterized hematopoletic parameters in GCV-treated Col2.3DeltaTK mice, and we show that after treatment transgenic animals lose lymphoid, erythroid, and myeloid progenitors in the bone marrow, followed by decreases in the number of hematopoietic stem cells (HSCs). Together with the decrease in bone marrow hematopoiesis, active extramedullary hematopoiesis was observed in the spleen and liver, as measured by an increase in peripheral HSCs and active primary in vitro hematopoiesis. After withdrawal of GCV, osteoblasts reappeared in the bone compartment together with a recovery of medullary and decrease in extramedullary hematopoiesis. These observations directly demonstrate the role of osteoblasts in hematopoiesis and provide a model to study the interactions between the mesenchymal and hematopoietic compartments in the marrow. (C) 2004 by The American Society of Hematology.