EXPRESSION OF A MYELIN BASIC-PROTEIN GENE IN TRANSGENIC SHIVERER MICE - CORRECTION OF THE DYSMYELINATING PHENOTYPE
EXPRESSION OF A MYELIN BASIC-PROTEIN GENE IN TRANSGENIC SHIVERER MICE - CORRECTION OF THE DYSMYELINATING PHENOTYPE
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DOI：
10.1016/0092-8674(87)90248-0
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发表时间：
1987-02-27
期刊：
影响因子：
64.5
通讯作者：
HOOD, L
中科院分区：
文献类型：
--
作者：
READHEAD, C;POPKO, B;HOOD, L
常染色体隐性突变寒战(SHI)纯合子小鼠缺乏髓鞘碱性蛋白(MBP)，并表现出独特的行为模式，包括震颤(颤抖)、抽搐和早期死亡。我们之前已经证明，颤抖的小鼠编码MBP的基因有部分缺失。我们现在已经将野生型MBP基因通过显微注射到受精卵中导入了寒战小鼠的胚系。导入基因纯合的转基因寒战小鼠的MBP mRNA和蛋白水平约为正常的25%，并产生主要致密线条的致密髓鞘。利用包含4kb的5‘’侧翼序列和1kb的3‘’侧翼序列的基因组MBP粘粒克隆，实现了MBP基因的正确时空表达。此外，还有由不同的RNA剪接模式产生的四种不同形式的MBP。这些纯合子转基因颤抖小鼠不再颤抖，也不会过早死亡。
Mice homozygous for the autosomal recessive mutation shiverer (shi) lack myelin basic protein (MBP) and exhibit a distinct behavioral pattern including tremors (shivering), convulsions, and early death. We have previously demonstrated that shiverer mice have a partial deletion in the gene encoding MBP. We now have introduced the wild-type MBP gene into the germ line of shiverer mice by microinjection into fertilized eggs. Transgenic shiverer mice homozygous for the introduced gene have MBP mRNA and protein levels that are approximately 25% of normal, and produce compacted myelin with major dense lines. Correct temporal and spatial expression of the MBP gene is achieved with a genomic MBP cosmid clone containing 4 kb of 5'' flanking sequence and 1 kb of 3'' flanking sequence. Moreover, the four different forms of MBP produced by alternative patterns of RNA splicing are present. These homnozygous transgenic shiverer mice no longer shiver nor die prematurely.