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Gene Array Data from p0 Mouse pup; ascending and descending aortas; fibulin-4 knockout and control

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Fibulin-4 plays an essential role in elastic fiber formation, though it's exact function is unclear. Mice lacking the fibulin-4 gene develop cutis laxa with thoracic aortic aneurysms and have narrowed descending aortic diamaters, dying shortly after birth. Another model that disrupt elastic fiber formation, elastin gene knockeds, are also perinatally lethal and have narrowed descending aortas but do not develop thoracic aneurysms. We hypothesized that there may be altered gene expression to explain the altered anatomy based on aortic tissue location we observed, which may provide therapeutic target(s) Ascending and descending aortas of p0 mouse pups were dissected, pooled in groups of eight, and homogenized to isolate RNA and we used microarrays on the pooled samples to identify genes that had expression significantly changed.

Fibulin-4(纤连蛋白-4)在弹性纤维形成过程中发挥关键作用,但其确切生物学功能尚未明确。敲除fibulin-4基因的小鼠可出现皮肤松弛症,伴发胸主动脉瘤,同时降主动脉管径变窄,幼崽于出生后短时间内死亡。另一种可破坏弹性纤维形成的模型——弹性蛋白基因敲除小鼠,同样表现为围产期致死,降主动脉管径变窄,但不会形成胸主动脉瘤。基于我们观察到的主动脉组织解剖结构异常,我们提出假说:存在基因表达改变以解释该解剖学变化,该发现或可提供潜在治疗靶点。我们对出生后0天(p0)的小鼠幼崽的升主动脉与降主动脉进行解剖分离,每8只样本分为一组进行混合,随后通过匀浆提取总RNA,并利用混合样本开展基因芯片(microarrays)检测,以筛选出表达水平发生显著变化的基因。

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