A myelin proteolipid protein-LacZ fusion protein is developmentally regulated and targeted to the myelin membrane in transgenic mice.
A myelin proteolipid protein-LacZ fusion protein is developmentally regulated and targeted to the myelin membrane in transgenic mice.
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DOI：
10.1083/jcb.123.2.443
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发表时间：
1993-10
期刊：
影响因子：
--
通讯作者：
Macklin WB
中科院分区：
文献类型：
--
作者：
Wight PA;Duchala CS;Readhead C;Macklin WB
转基因小鼠用携带鼠髓鞘蛋白脂质蛋白（PLP）基因的一部分的融合基因产生，包括第一内含子，融合到E。coliLacZ基因。衍生出三个转基因品系，并且所有品系在中枢神经系统白色物质中表达转基因，如通过用于检测β-半乳糖苷酶活性的组织化学测定所测量的。PLP-LacZ转基因表达在空间和时间上都受到调节，与内源性PLP表达一致。此外，转基因表达特异性少突胶质细胞从原代混合神经胶质细胞培养物制备的转基因小鼠的大脑，并出现在体外发育调节以及。转基因表达发生在胚胎中，大概是在前或非髓鞘细胞，而广泛地在整个外周神经系统和中枢神经系统的非常离散的区域内。令人惊讶的是，在这些转基因动物中，β-半乳糖苷酶活性主要位于髓鞘中，这表明存在于PLP-LacZ基因产物中的PLP的NH 2-末端13个氨基酸足以使蛋白质靶向髓鞘膜。因此，PLP基因的前半部分含有足以指导空间和时间基因调控的序列，并编码在将蛋白质靶向髓鞘膜中重要的氨基酸。
Transgenic mice were generated with a fusion gene carrying a portion of the murine myelin proteolipid protein (PLP) gene, including the first intron, fused to the E. coli LacZ gene. Three transgenic lines were derived and all lines expressed the transgene in central nervous system white matter as measured by a histochemical assay for the detection of beta-galactosidase activity. PLP-LacZ transgene expression was regulated in both a spatial and temporal manner, consistent with endogenous PLP expression. Moreover, the transgene was expressed specifically in oligodendrocytes from primary mixed glial cultures prepared from transgenic mouse brains and appeared to be developmentally regulated in vitro as well. Transgene expression occurred in embryos, presumably in pre- or nonmyelinating cells, rather extensively throughout the peripheral nervous system and within very discrete regions of the central nervous system. Surprisingly, beta- galactosidase activity was localized predominantly in the myelin in these transgenic animals, suggesting that the NH2-terminal 13 amino acids of PLP, which were present in the PLP-LacZ gene product, were sufficient to target the protein to the myelin membrane. Thus, the first half of the PLP gene contains sequences sufficient to direct both spatial and temporal gene regulation and to encode amino acids important in targeting the protein to the myelin membrane.
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影响因子：
64.5
作者：
HARPOLD, MM;EVANS, RM;DARNELL, JE
通讯作者：
DARNELL, JE
影响因子：
2.9
作者：
ENG, LF;CHAO, FC;TAVASTSTJERNA, MG
通讯作者：
TAVASTSTJERNA, MG
影响因子：
5.3
作者：
GARDINIER, MV;MACKLIN, WB;DEININGER, PL
通讯作者：
DEININGER, PL
DOI：
10.1073/pnas.84.24.8869
发表时间：
1987-12-01
影响因子：
11.1
作者：
BORNSTEIN, P;MCKAY, J;GELINAS, RE
通讯作者：
GELINAS, RE
DOI：
10.1083/jcb.102.2.384
发表时间：
1986-02
期刊：
The Journal of cell biology
影响因子：
--
作者：
Dubois-Dalcq M;Behar T;Hudson L;Lazzarini RA
通讯作者：
Lazzarini RA