Relative transgene expression frequencies in homozygous versus hemizygous transgenic mice

被引:5
作者
Chang, Su-Ping [1 ]
Opsahl, Margaret L. [2 ,3 ]
Whitelaw, C. Bruce A. [2 ,3 ]
Morley, Steven D. [4 ]
West, John D. [1 ]
机构
[1] Univ Edinburgh, Genes & Dev Grp, Ctr Integrat Physiol, Sch Clin Sci, Edinburgh EH8 9XD, Midlothian, Scotland
[2] Univ Edinburgh, Div Dev Biol, Roslin Inst, Roslin EH25 9PS, Midlothian, Scotland
[3] Univ Edinburgh, Royal Dick Sch Vet Studies, Roslin EH25 9PS, Midlothian, Scotland
[4] Univ Edinburgh, Sch Med, Clin Biochem Sect, Div Hlth Sci, Edinburgh EH16 1SB, Midlothian, Scotland
基金
英国生物技术与生命科学研究理事会;
关键词
Transgenic mice; Transgene inactivation; Transgene silencing; Position effect variegation; Mosaic transgene expression; POSITION EFFECT VARIEGATION; STEM-CELL ACTIVITY; ADRENAL-CORTEX; CORNEAL EPITHELIUM; MOUSE; CHIMERAS; LINEAGE; LOCUS; GENE; MAINTENANCE;
D O I
10.1007/s11248-013-9732-5
中图分类号
Q5 [生物化学];
学科分类号
071010 ; 081704 ;
摘要
We have used a simple binomial model of stochastic transgene inactivation at the level of the chromosome or transgene, rather than the cellular level, for the analysis of two mouse transgenic lines that show variegated patterns of expression. This predicts the percentages of cells that express one, both or neither alleles of the transgene in homozygotes from the observed percentages of cells, which express the transgene in hemizygotes. It adequately explained the relationship between the numbers of cells expressing the transgene in hemizygous and homozygous mosaic 21OH/LacZ mouse adrenals and mosaic BLG/7 mouse mammary glands. The binomial model also predicted that a small proportion of cells in mosaic mammary glands of BLG/7 homozygotes would express both BLG/7 alleles but published data indicated that all cells expressing the transgene showed monoallelic expression. Although it didn't fit all of the BLG/7 data as precisely as a more complex model, which used several ad hoc assumptions to explain these results, the simple binomial model was able to explain the relationship in observed transgene expression frequencies between hemizygous and homozygous mosaic tissues for both 21OH/LacZ and BLG/7 mice. It may prove to be a useful general model for analysing other transgenic animals showing mosaic transgene expression.
引用
收藏
页码:1143 / 1154
页数:12
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