Journal
MECHANISMS OF DEVELOPMENT
Volume 119, Issue -, Pages S97-S101Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/S0925-4773(03)00099-6
Keywords
Sox2; Cre; recombinase; 1oxP; Mox2 (MORE); sonic hedgehog; R26R; Z/AP; epiblast; visceral endoderm; extraembryonic tissue
Categories
Funding
- NICHD NIH HHS [HD30249] Funding Source: Medline
- NIDDK NIH HHS [DK54364] Funding Source: Medline
- NINDS NIH HHS [NS33642] Funding Source: Medline
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We have generated a transgenic line that expresses the Cre gene product under the regulation of a 12.5 kb upstream regulatory sequence from the Sox2 gene. Using a R26R reporter line, we show that this transgenic line induces recombination in all epiblast cells by embryonic day ( E) 6.5 but little or no activity in other extraembryonic cell types at this time. When crossed to a conditional allele of the Sonic hedgehog gene ( Shh(c)), all Sox2Cre; Shh(n)/Shh(c) embryos displayed a phenotype indistinguishable from that of the Shh null mutant. Sox2Cre functioned more efficiently in epiblast-mediated recombination than the Mox2Cre ( MORE) transgenic line, which has also been shown to drive Cre-mediated recombination exclusively in the embryonic component of the early mouse embryo. Although most MORE; shh(h)/shh(c) embryos have a shh hull phenotype, 33% displayed a milder skeletal phenotype, most likely result of incomplete recombination at egg cylinder stages. In agreement with these findings, Sox2Cre was active earlier and Sox2Cre-mediated recombination was more advanced than MORE-mediated recombination at early gastrulation stages. The Sox2Cre line is likely to be more effective in generating complete, epiblast-specific removal of gene activity, and the mosaic activity of the MORE line will be helpful in generating partial loss-of-function phenotypes in the embryo-proper. (C) 2003 Elsevier Science Ireland Ltd. All rights reserved.
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