Doyle Glenn A, Rebecca Sheng X, Lin Sharon S J, Press Danielle M, Grice Dorothy E, Buono Russell J, Ferraro Thomas N, Berrettini Wade H
The Center for Neurobiology and Behavior, Department of Psychiatry, University of Pennsylvania, Philadelphia, Pennsylvania 19104, United States.
Gene. 2007 Feb 15;388(1-2):135-47. doi: 10.1016/j.gene.2006.10.017. Epub 2006 Nov 1.
The mouse mu-opioid receptor gene, Oprm1, is recognized currently to contain 17 alternatively spliced exons that generate 24 splice variants encoding at least 11 morphine-binding isoforms of the receptor. Here, we identify three new MOR splice variants that contain a previously undescribed exon, exon 18, and provide evidence that they are expressed in two mouse strains. The transcripts containing the newly identified exon 18 encode two new putative mu-opioid receptor isoforms, MOR-1V and MOR-1W. In mouse Oprm1, exon 18 is located between the described exons 10 and 6. Exon 18 appears to be conserved in the rat genome between exons 4 and 7. A BLAST search of the non-redundant GenBank database suggests that human OPRM1 may also contain exon 18. Analysis of mouse brain mRNA by RT-PCR suggests that MOR-1Vii transcripts are expressed in all areas of the brain analyzed, whereas expression of MOR-1Vi transcripts was restricted to thalamus and striatum. MOR-1W transcripts are expressed most highly in the hypothalamus, thalamus and striatum. In summary, we have identified three brain expressed, alternatively spliced mouse MOR splice variants containing a novel exon and encoding new putative MOR isoforms, MOR-1V and MOR-1W.
小鼠μ-阿片受体基因Oprm1目前被认为包含17个可变剪接外显子,这些外显子产生24种剪接变体,编码至少11种该受体的吗啡结合亚型。在此,我们鉴定出三种新的MOR剪接变体,它们包含一个以前未描述的外显子,即外显子18,并提供证据表明它们在两种小鼠品系中表达。包含新鉴定的外显子18的转录本编码两种新的假定μ-阿片受体亚型,即MOR-1V和MOR-1W。在小鼠Oprm1中,外显子18位于已描述的外显子10和6之间。外显子18在大鼠基因组中似乎在外显子4和7之间保守。对非冗余GenBank数据库的BLAST搜索表明,人类OPRM1可能也包含外显子18。通过RT-PCR对小鼠脑mRNA的分析表明,MOR-1Vii转录本在所有分析的脑区中均有表达,而MOR-1Vi转录本的表达仅限于丘脑和纹状体。MOR-1W转录本在下丘脑、丘脑和纹状体中表达最高。总之,我们鉴定出三种在脑中表达的、可变剪接的小鼠MOR剪接变体,它们包含一个新外显子并编码新的假定MOR亚型,即MOR-1V和MOR-1W。