Deletion of the core-H region in mice abolishes the expression of three proximal odorant receptor genes in cis
Deletion of the core-H region in mice abolishes the expression of three proximal odorant receptor genes in cis
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DOI：
10.1073/pnas.0706544105
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发表时间：
2007-12-11
影响因子：
11.1
通讯作者：
Sakano, Hitoshi
中科院分区：
文献类型：
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作者：
Nishizumi, Hirofurni;Kurnasaka, Kouhei;Sakano, Hitoshi
我们之前报道了一个2.1 kb的同源(H)序列，在小鼠和人类之间保守，调节转基因小鼠的气味受体（OR）基因MOR28。在此，我们利用斑马鱼胚胎瞬时表达系统，将H的基本序列缩小到124bp的核心。在小鼠中进行的转基因实验表明，core-H序列足以赋予MOR28小基因的表达。对核心H区进行的缺失和突变分析显示，两个同源结构域序列对H增强子活性至关重要。核心- h的靶向缺失顺式地消除了三个近端OR基因MOR28、MOR10和MOR83的表达，表明在下游区域存在另一个基因座控制区/增强子，该基因座控制区/增强子调节同一MOR28簇中的四个远端OR基因。在杂合小鼠中，突变等位基因的H-表型未被反式中野生型H+等位基因所拯救。
We have previously reported that a 2.1-kb homology (H) sequence, conserved between mouse and human, regulates the odorant receptor (OR) gene MOR28 in transgenic mice. Here, we narrowed down the essential sequences of the H to a core of 124 bp by using a transient expression system in zebrafish embryos. Transgenic experiments in mice demonstrated that the core-H sequence is sufficient to endow expression of the MOR28 minigene. Deletion and mutation analyses of the core-H region revealed two homeodomain sequences to be essential for the H enhancer activity. Targeted deletion of the core-H abolished expression of three proximal OR genes, MOR28, MOR10, and MOR83, in cis, indicating the presence of another locus control region/enhancer in the downstream region, that regulates four distal OR genes in the same MOR28 cluster. In the heterozygous mice, the H- phenotype of the mutant allele was not rescued by the wild-type H+ allele in trans.