Gene organization and transcription of duplicated MBP genes of myelin deficient (shi(mld)) mutant mouse.
Gene organization and transcription of duplicated MBP genes of myelin deficient (shi(mld)) mutant mouse.
复制标题
髓磷脂缺陷 (shi(mld)) 突变小鼠的重复 MBP 基因的基因组织和转录。
作者：
H. Okano;T. Tamura;M. Miura;A. Aoyama;K. Ikenaka;M. Oshimura;K. Mikoshiba
一种遗传性髓鞘形成障碍突变，称为髓鞘缺乏（shi（mld）），其特征在于髓鞘碱性蛋白（MBP）表达减少。在shi（mld）中，MBP基因是重复的，其表达减少主要由mRNA水平决定。我们的特点是结构和功能的重复MBP基因的启动子区的shi（mld）。在含有shi（mld）中的重复MBP基因的启动子区域的λ克隆中，一个（基因1）具有与对照小鼠相同的限制性酶切图谱，但另一个（基因2）在启动子的远端部分具有重排。shi（mld）的两个重复MBP基因的第一外显子上游的712 bp核苷酸序列与对照完全一致。通过使用HeLa全细胞提取物的体外径流试验测量的shi（mld）各基因的1.3-kb 5′侧翼区的启动子活性与对照MPB基因的启动子活性无法区分。染色体定位原位杂交表明，重复MBP基因位于彼此接近的18号染色体的远端部分。一个重组事件，包括倒位似乎发生在基因1和其可能的关系，MBP的表达减少进行了讨论。
A hereditary dysmyelinating mutation, named myelin deficient (shi(mld)), is characterized by reduced expression of myelin basic protein (MBP). In shi(mld), the MBP gene is duplicated and its reduced expression is mainly determined by the level of mRNA. We have characterized the structure and function of the promoter regions of the duplicated MBP genes in shi(mld). Among the lambda clones containing promoter regions of the duplicated MBP genes in shi(mld), one (gene 1) had the same restriction enzyme pattern as that in control mice, but another (gene 2) had a rearrangement on a distal part of the promoter. A 712‐bp nucleotide sequence upstream of the first exons of both of the duplicated MBP genes of shi(mld) was completely consistent with that of the control. Promoter activities of 1.3‐kb 5′‐flanking regions from respective genes of shi(mld) measured by in vitro run‐off assay using HeLa whole‐cell extracts were indistinguishable from that of the control MPB gene. Chromosomal mapping by in situ hybridization suggested that the duplicated MBP genes were located closely to each other at the distal part of chromosome 18. A recombinational event including the inversion seemed to have occurred within gene 1 and its possible relationship to the reduced expression of MBP is discussed.