Growth plate compressions and altered hematopoiesis in collagen X null mice.

Growth plate compressions and altered hematopoiesis in collagen X null mice.
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DOI:
10.1083/jcb.149.4.983
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发表时间:
2000-05-15
期刊:
The Journal of cell biology
影响因子:
--
通讯作者:
Jacenko O
Jacenko O
中科院分区:
其他
文献类型:
--
作者:
Gress CJ;Jacenko O

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在X胶原蛋白缺失的小鼠中观察到一种可变的骨骼-造血表型,这反映了具有X胶原蛋白显性干扰突变的转基因(Tg)小鼠的缺陷(Jacenko, O., P. LuValle,和B.R. Olsen, 1993)。大自然。365:56 - 61)。具体而言,在出生后第3周,约10.8%的零突变体出现围产期死亡,另一部分在12周时出现围产期死亡。在围产期致死性突变体中,生长板被压缩,小梁骨减少,骨髓中造血发育不全和红细胞充盈的血管窦明显。淋巴器官,减少到对照组的80%,显示出结构和淋巴细胞含量的改变。在胸腺中,皮质CD3+/CD4+/CD8+淋巴细胞的缺乏与骨髓无法补充成熟T细胞一致。脾脏中,未改变的T细胞分布与IgD+/B220+ B细胞弥漫性染色相结合,其减少在组织不良的淋巴结节中表现突出。小动脉周围淋巴鞘周围的脾巨噬细胞无序排列和红髓耗竭进一步补充了Tg围产期致死表型。此外,在所有小鼠中均可见轻微的生长板压迫和造血变化。来自Tg和null小鼠的数据表明,在观察到的骨骼造血缺陷中,X胶原功能受到破坏,并表明软骨肥大和软骨内骨骼生成可能有助于造血细胞分化的骨髓微环境先决条件。
A variable skeleto-hematopoietic phenotype was observed in collagen X null mice which mirrored the defects in transgenic (Tg) mice with dominant interference collagen X mutations (Jacenko, O., P. LuValle, and B.R. Olsen. 1993. Nature. 365:56–61). Specifically, perinatal lethality was seen in ∼10.8% of null mutants at week three after birth, and in another subset by 12 wk. In perinatal lethal mutants, growth plates were compressed, trabecular bone reduced, and hematopoietic aplasia and erythrocyte-filled vascular sinusoids were apparent in marrows. Lymphatic organs, reduced to ∼80% that of controls, displayed altered architecture and lymphocyte content. In thymuses, a paucity of cortical CD3+/CD4+/CD8+ lymphocytes was consistent with the marrow's inability to replenish maturing T cells. In spleens, an unaltered T cell distribution was coupled with diffuse staining for IgD+/B220+ B cells, whose reduction was prominent in poorly organized lymphatic nodules. Disorderly arrays of splenic macrophages surrounding periarteriolar lymphatic sheaths and a red pulp depletion further complemented the Tg perinatal lethal phenotype. Moreover, subtle growth plate compressions and hematopoietic changes were seen in all null mice. Data from Tg and null mice implicate the disruption of collagen X function in the observed skeleto-hematopoietic defects, and suggest that hypertrophic cartilage and endochondral skeletogenesis may contribute to the marrow microenvironment prerequisite for blood cell differentiation.
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