Sequence and chromosomal context effects on variegated expression of keratin 5/lacZ constructs in stratified epithelia of transgenic mice.
Sequence and chromosomal context effects on variegated expression of keratin 5/lacZ constructs in stratified epithelia of transgenic mice.
复制标题
序列和染色体环境对转基因小鼠分层上皮中角蛋白 5/lacZ 构建体杂色表达的影响。
作者：
Á. Ramírez;E. Milot;I. Ponsa;C. Marcos;A. Page;M. Santos;J. Jorcano;M. Vidal
转基因座在哺乳动物中的表达通常以异细胞方式发生，导致多样化的表达模式。我们研究了染色体整合位点、拷贝数和转录激活序列对转基因小鼠复层上皮中角蛋白5-lacZ（K5 Z）构建体杂色的影响。这些小鼠中的lacZ表达总是镶嵌的，并且每个细胞的β-gal活性通常在具有较高表达细胞比例的品系中较高。类似的构建体，其中cDNA被lacZ序列交换，没有显示杂色。此外，当一个强活性，nonvariegating构建共注射K5 Z，大多数转基因株系表现出几乎同质lacZ表达。在相同基因座插入的不同拷贝的转基因阵列（通过使用lox/Cre系统获得）的比较表明，拷贝数的减少不会导致表达转基因的细胞比例的增加。最后，在大多数变异或nonexpressing线的转基因位于中间位置和在端粒区的长染色体臂。这些发现表明K5 Z基因表达的可能性和效率取决于长范围染色体影响和转基因阵列中的序列。
The expression of transgene loci in mammals often occurs in a heterocellular fashion resulting in variegated patterns of expression. We have examined the effect of chromosomal integration site, copy number, and transcriptionally activating sequences on the variegation of a keratin 5-lacZ (K5Z) construct in the stratified epithelia of transgenic mice. lacZ expression in these mice is always mosaic, and the beta-gal activity per cell is usually higher in the lines with a higher proportion of expressing cells. Similar constructs, in which cDNAs were exchanged by lacZ sequences, showed no variegation. Also, when a strongly active, nonvariegating construct was coinjected with K5Z, most transgenic lines showed an almost homogeneous lacZ expression. The comparison of transgene arrays of different copies inserted at the same locus (obtained by using a lox/Cre system) showed that the reduction of copy number does not lead to an increase in the proportion of cells that express the transgene. Finally, in most of the variegating or nonexpressing lines the transgenes were located both at intermediate positions and at peritelomeric regions in the long chromosome arms. These findings suggest that the probability and efficiency of expression of K5Z genes depend on both long range chromosomal influences and on sequences in the transgene array.
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DOI：
10.1073/pnas.91.19.8861
发表时间：
1994-09-13
影响因子：
11.1
作者：
HANISH, JP;YANOWITZ, JL;DELANGE, T
通讯作者：
DELANGE, T
DOI：
10.1073/pnas.88.3.1049
发表时间：
1991-02
影响因子：
11.1
作者：
L. Manuelidis
通讯作者：
L. Manuelidis
影响因子：
20.3
作者：
Bouhassira, EE;Westerman, K;Leboulch, P
通讯作者：
Leboulch, P
小鼠类固醇21-羟化酶/β-半乳糖苷酶转基因的多样化表达表明肾上腺皮质细胞的向心迁移。
DOI：
10.1210/mend.10.5.8732689
发表时间：
1996
期刊：
Molecular endocrinology (Baltimore, Md.)
影响因子：
--
作者：
Morley,SD;Viard,I;Chung,BC;Ikeda,Y;Parker,KL;Mullins,JJ
通讯作者：
Mullins,JJ
转录增强子以顺式作用抑制位置效应杂色。
影响因子：
10.5
作者：
Walters,MC;Magis,W;Fiering,S;Eidemiller,J;Scalzo,D;Groudine,M;Martin,DI
通讯作者：
Martin,DI