Pyrski M, Xu Z, Walters E, Gilbert D J, Jenkins N A, Copeland N G, Margolis F L
Department of Anatomy and Neurobiology, School of Medicine, University of Maryland at Baltimore, Baltimore, Maryland 21201, USA.
J Neurosci. 2001 Jul 1;21(13):4637-48. doi: 10.1523/JNEUROSCI.21-13-04637.2001.
Reporter gene expression in the olfactory epithelium of H-lacZ6 transgenic mice mimics the cell-selective expression pattern known for some odorant receptor genes. The transgene construct in these mice consists of the lacZ coding region, driven by the proximal olfactory marker protein (OMP) gene promoter, and shows expression in a zonally confined subpopulation of olfactory neurons. To address mechanisms underlying the odorant receptor-like expression pattern of the lacZ construct, we analyzed the transgene-flanking region and identified OR-Z6, the first cloned odorant receptor gene that maps to mouse chromosome 6. OR-Z6 bears the highest sequence similarity (85%) to a human odorant receptor gene at the syntenic location on human chromosome 7. We analyzed the expression pattern of OR-Z6 in olfactory tissues of H-lacZ6 mice and show that it bears strong similarities to that mapped for beta-galactosidase. Expression of both genes in olfactory neurons is primarily restricted to the same medial subregion of the olfactory epithelium. Axons from both neuronal subpopulations project to the same ventromedial aspect of the anterior olfactory bulbs. Furthermore, colocalization analyses in H-lacZ6 mice demonstrate that OR-Z6-reactive glomeruli receive axonal input from lacZ-positive neurons as well. These results suggest that the expression of both genes is coordinated and that transgene expression in H-lacZ6 mice is regulated by locus-dependent mechanisms.
在H-lacZ6转基因小鼠的嗅觉上皮中,报告基因的表达模拟了一些气味受体基因已知的细胞选择性表达模式。这些小鼠中的转基因构建体由近端嗅觉标记蛋白(OMP)基因启动子驱动的lacZ编码区组成,并在嗅觉神经元的一个区域受限的亚群中表达。为了探究lacZ构建体类似气味受体表达模式的潜在机制,我们分析了转基因侧翼区域,并鉴定出OR-Z6,这是第一个定位到小鼠6号染色体上的克隆气味受体基因。OR-Z6与人类7号染色体上同线性位置的一个人类气味受体基因具有最高的序列相似性(85%)。我们分析了OR-Z6在H-lacZ6小鼠嗅觉组织中的表达模式,结果表明它与β-半乳糖苷酶的定位模式具有很强的相似性。这两个基因在嗅觉神经元中的表达主要局限于嗅觉上皮的同一内侧亚区域。来自这两个神经元亚群的轴突都投射到前嗅球的同一腹内侧区域。此外,对H-lacZ6小鼠的共定位分析表明,对OR-Z6有反应的肾小球也接收来自lacZ阳性神经元的轴突输入。这些结果表明这两个基因的表达是协调的,并且H-lacZ6小鼠中的转基因表达受基因座依赖性机制调控。