Akowitz A A, Barbarese E, Scheld K, Carson J H
Genetics. 1987 Jul;116(3):447-64. doi: 10.1093/genetics/116.3.447.
The mld mutation on chromosome 18 in the mouse is a putative allele of the shiverer (shi) mutation. We have analyzed the structure of myelin basic protein (MBP) gene sequences in mld DNA by restriction mapping of genomic DNA. The results indicate that the mld chromosome carries two copies of the MBP structural gene, one of which is intact and one of which is interrupted. Genetic analysis indicates that the interrupted gene is close to the intact MBP structural gene and cosegregates with the mld mutation. We have also analyzed the levels of MBP polypeptides and MBP-specific mRNA in wild-type, homozygous and heterozygous shiverer and mld mice and in mice carrying both mutations. The results indicate that both shi and mld are cis-acting codominant mutations that cause severely reduced steady state levels of MBP-specific mRNA and MBP polypeptides in the brain. We have analyzed the total number of oligodendrocytes and the number of MBP-positive oligodendrocytes in mld and shi brain primary cultures. In shi cultures, none of the oligodendrocytes expresses MBP. However, in mld cultures, approximately 5% of the oligodendrocytes express MBP. The nature of the "revertant" mld oligodendrocytes is not known.
小鼠18号染色体上的mld突变是颤抖（shi）突变的一个假定等位基因。我们通过基因组DNA的限制性图谱分析了mld DNA中髓鞘碱性蛋白（MBP）基因序列的结构。结果表明，mld染色体携带两个MBP结构基因拷贝，其中一个是完整的，另一个是中断的。遗传分析表明，中断的基因靠近完整的MBP结构基因，并与mld突变共分离。我们还分析了野生型、纯合和杂合颤抖及mld小鼠以及携带两种突变的小鼠中MBP多肽和MBP特异性mRNA的水平。结果表明，shi和mld都是顺式作用的共显性突变，导致大脑中MBP特异性mRNA和MBP多肽的稳态水平严重降低。我们分析了mld和shi脑原代培养物中少突胶质细胞的总数以及MBP阳性少突胶质细胞的数量。在shi培养物中，没有少突胶质细胞表达MBP。然而，在mld培养物中，约5%的少突胶质细胞表达MBP。“回复”的mld少突胶质细胞的性质尚不清楚。
