Transcriptional profiling of the megabladder mouse: a unique model of bladder dysmorphogenesis.
Transcriptional profiling of the megabladder mouse: a unique model of bladder dysmorphogenesis.
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大膀胱小鼠的转录谱：膀胱畸形发生的独特模型。
DOI：
10.1002/dvdy.21391
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发表时间：
2008
期刊：
影响因子：
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通讯作者：
McHugh,KirkM
中科院分区：
文献类型：
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作者：
Singh,Sunita;Robinson,Melissa;Ismail,Ihab;Saha,Monalee;Auer,Herbert;Kornacker,Karl;Robinson,MichaelL;Bates,CarltonM;McHugh,KirkM
我们实验室最近的研究发现了一种梗阻性肾病突变小鼠模型，命名为“mgb for megabladder”。纯合mgb小鼠（mgb−/−）由于缺乏膀胱平滑肌分化而在子宫内出现下尿路梗阻。这种缺陷是随机转基因插入/易位到 11 号和 16 号染色体的结果。转录谱鉴定出位于 16 号染色体易位片段上的一组显着过度表达的基因产物，其中包括尾加压素 II 相关肽 (Urp)，该肽在发育中的 mgb−/− 膀胱中优先过度表达。 mgb 微阵列数据的通路分析表明至少 60 种与平滑肌发育相关的基因产物存在失调。总之，本研究结果表明，控制正常平滑肌发育的分子途径在mgb−/−膀胱中发生了严重改变，并提供了Urp可能在膀胱平滑肌发育中发挥关键作用的第一个证据。发展动力学 237:170–186, 2008。© 2007 Wiley-Liss, Inc.
Recent studies in our lab identified a mutant mouse model of obstructive nephropathy designatedmgbfor megabladder. Homozygoticmgbmice (mgb−/−) develop lower urinary tract obstruction in utero due to a lack of bladder smooth muscle differentiation. This defect is the result of a random transgene insertion/translocation into chromosomes 11 and 16. Transcriptional profiling identified a significantly over‐expressed cluster of gene products located on the translocated fragment of chromosome 16 including urotensin II‐related peptide (Urp), which was shown to be preferentially over‐expressed in developingmgb−/− bladders. Pathway analysis ofmgbmicroarray data indicated dysregulation of at least 60 gene products associated with smooth muscle development. In conclusion, the results of this study indicate that the molecular pathways controlling normal smooth muscle development are severely altered inmgb−/− bladders, and provide the first evidence that Urp may play a critical role in bladder smooth muscle development. Developmental Dynamics 237:170–186, 2008. © 2007 Wiley‐Liss, Inc.