Okano H, Ikenaka K, Mikoshiba K
Division of Regulation of Macromolecular Function, Osaka University, Japan.
EMBO J. 1988 Nov;7(11):3407-12. doi: 10.1002/j.1460-2075.1988.tb03214.x.
The myelin deficient shimld mouse is an autosomal recessive mutant, characterized by hypomyelination in the central nervous system. The expression of the myelin basic protein (MBP) gene is inhibited transcriptionally. The MBP gene is duplicated tandemly in mld, and exons 3 to 7 of the upstream copy is inverted. In the present studies, we determined the approximate position of the 5' boundary and the nucleotide sequence surrounding the 3' boundary of the inversion and found a number of sequences homologous to the switching regions of mouse immunoglobulin heavy chain gene and J regions of human T cell receptor genes. Antisense RNA complementary to exons 3 and 7, which correspond to the inverted segment, was detected by RNase protection studies. This abnormal transcript was also shown to elongate through the inverted segment to reach the transcription initiation site of the downstream gene.
髓磷脂缺陷型希姆尔德小鼠是一种常染色体隐性突变体，其特征是中枢神经系统髓鞘形成不足。髓磷脂碱性蛋白（MBP）基因的表达在转录水平受到抑制。MBP基因在mld小鼠中串联重复，上游拷贝的外显子3至7发生了倒位。在本研究中，我们确定了倒位5'边界的大致位置以及围绕3'边界的核苷酸序列，并发现了一些与小鼠免疫球蛋白重链基因的转换区和人类T细胞受体基因的J区同源的序列。通过核糖核酸酶保护研究检测到了与对应于倒位片段的外显子3和7互补的反义RNA。还显示这种异常转录本会延伸通过倒位片段到达下游基因的转录起始位点。
