Differential gene dosage effects of Ad4BP/SF-1 on target tissue development
Differential gene dosage effects of Ad4BP/SF-1 on target tissue development
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DOI：
10.1016/j.bbrc.2006.01.058
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发表时间：
2006-03-24
影响因子：
3.1
通讯作者：
Morohashi, K
中科院分区：
文献类型：
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作者：
Futchiyah;Zubair, M;Morohashi, K
Ad 4 BP/SF-1（NR 5A 1）被鉴定为下丘脑-垂体-性腺和-肾上腺轴的关键调节剂。功能丧失研究表明，Ad 4 BP/SF-1对这些组织和脾脏的发育至关重要。在这里，我们用携带双启动子和Tet-off系统的BAC重组体产生转基因小鼠。这些重组体有可能在表达内源性Ad 4 BP/SF-1的组织中表达lacZ和Ad 4 BP/SF-1。然而，Ad 4 BP/SF-1的蛋白水平在转基因小鼠的组织中变化，并且可能因此靶组织受到差异影响。将BAC转基因小鼠用于拯救Ad 4 BP/SF-1 KO小鼠。有趣的是，小鼠成功地挽救了性腺和脾脏，但未能挽救肾上腺。这种变化可能部分取决于组织中的蛋白质表达水平，部分取决于对基因剂量的不同敏感性。(c)2006年爱思唯尔公司All rights reserved.
Ad4BP/SF-1 (NR5A1) was identified as a key regulator of the hypothalamus-pituitary-gonadal and -adrenal axes. Loss-of-function studies revealed that Ad4BP/SF-1 is essential for the development of these tissues and spleen. Here, we generated transgenic mouse with BAC recombinants carrying a dual promoter and Tet-off system. These recombinants have a potential to express lacZ and Ad4BP/SF-1 in the tissues where endogenous Ad4BP/SF-1 is expressed. However, protein level of Ad4BP/SF-1 varied among the tissues of the transgenic mice and probably thereby the target tissues are affected differentially. The BAC-transgenic mice were applied to rescue Ad4BP/SF-1 KO mouse. Interestingly, the mice successfully rescued the gonad and spleen but failed to rescue the adrenal gland. This variation might be dependent on in part the protein expression levels among the tissues and in part on differential sensitivities to the gene dosage. (c) 2006 Elsevier Inc. All rights reserved.