Microarray analysis of Myf5-/-:MyoD-/- hypoplastic mouse lungs reveals a profile of genes involved in pneumocyte differentiation
Microarray analysis of Myf5-/-:MyoD-/- hypoplastic mouse lungs reveals a profile of genes involved in pneumocyte differentiation
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DOI：
10.14670/hh-22.483
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发表时间：
2007-05-01
影响因子：
2
通讯作者：
Kablar, B.
中科院分区：
文献类型：
--
作者：
Baguma-Nibasheka, M.;Angka, H. E.;Kablar, B.
胎儿呼吸样运动（FBM）对于正常的肺部生长和肺细胞分化很重要。在肌源性小鼠胚胎（称为 Myf5-/-:MyoD-/-，完全缺乏骨骼肌组织和 FBM）中，II 型肺细胞无法分化为负责气体交换的 I 型肺细胞，胎儿在出生时死于窒息。使用寡核苷酸微阵列，我们比较了 Myf5-/-: MyoD-/- 胚胎肺部的基因表达与正常足月肺部的基因表达。在双突变胚胎的肺部，有 9 个基因上调，54 个基因下调至少 2 倍。由于许多下调的基因与淋巴细胞功能有关，因此采用免疫组织化学来研究胸腺和脾脏中的 T 细胞和 B 细胞成熟度。我们对正常淋巴细胞成熟度的发现表明，下调是双突变肺表型特有的，而不是其免疫系统特有的。免疫染色还揭示了下调基因的转录和生长因子（SATB1、c-Myb、CTGF）分布的改变，目前已知这些基因的敲除会导致胚胎或新生儿因呼吸衰竭而死亡。总之，微阵列分析似乎已经确定了可能参与肺细胞分化的基因谱，因此也确定了可能涉及 FBM 依赖性肺发育不全的机械化学信号转导途径的机制。
Fetal breathing-like movements (FBMs) are important in normal lung growth and pneumocyte differentiation. In amyogenic mouse embryos (designated as Myf5-/-:MyoD-/-, entirely lacking skeletal musculature and FBMs), type II pneumocytes fail to differentiate into type I pneumocytes, the cells responsible for gas exchange, and the fetuses die from asphyxia at birth. Using oligonucleotide microarrays, we compared gene expression in the lungs of Myf5-/-: MyoD-/- embryos to that in normal lungs at term. Nine genes were found to be up-regulated and 54 down-regulated at least 2-fold in the lungs of double-mutant embryos. Since many down-regulated genes are involved in lymphocyte function, immunohistochemistry was employed to study T- and B-cell maturity in the thymus and spleen. Our findings of normal lymphocyte maturity implied that the down-regulation was specific to the double-mutant lung phenotype and not to its immune system. Immunostaining also revealed altered distribution of transcription and growth factors (SATB1, c-Myb, CTGF) from down-regulated genes whose knockouts are now known to undergo embryonic or neonatal death secondary to respiratory failure. Together, it appears that microarray analysis has identified a profile of genes potentially involved in pneumocyte differentiation and therefore in the mechanisms that may be implicated in the mechanochemical signal transduction pathways underlying FBMs-dependent pulmonary hypoplasia.