Sequence and chromosomal context effects on variegated expression of keratin 5/lacZ constructs in stratified epithelia of transgenic mice.

Genetics
A RamírezM Vidal

Abstract

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 o...Continue Reading

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Citations

Feb 21, 2006·Biochimica Et Biophysica Acta·Roxana M LlanosJulian F B Mercer
Dec 23, 2006·Biochimica Et Biophysica Acta·Masahiro KawaharaTeruyuki Nagamune
Aug 31, 2004·Anais Da Academia Brasileira De Ciências·Oleg Serov, Irina Serova
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May 15, 2007·European Journal of Cell Biology·Borut KlopcicManfred Blessing
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Jul 9, 2002·Pigment Cell Research·Patricia Giraldo, Lluís Montoliu
Jul 18, 2002·The Journal of Biological Chemistry·Mirentxu SantosJosé L Jorcano

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