Kinetics of tamoxifen-regulated Cre activity in mice using a cartilage-specific CreER(T) to assay temporal activity windows along the proximodistal limb skeleton.
Cartilage differentiation occurs over a broad time range from early embryonic development, when the mesenchymal condensations that give rise to cartilage models for future bone first appear, and continuing through adult life, when there is ongoing maintenance of articular joint surfaces and re-activation of cartilage formation after fracture. The chondrogenic response also figures in the pathogenesis of degenerative and inflammatory joint diseases. We have generated a transgenic line expressing tamoxifen-dependent Cre recombinase that gives efficient recombination in the chondrogenic lineage, both during embryogenesis and postnatally, and provides a valuable tool for analysis of gene function selectively in chondrogenic cells using conditional genetic approaches. Because the cartilage model of the limb skeleton forms progressively in a proximodistal order during discrete, well-defined time periods, evaluation of the spatial extent of tamoxifen-induced recombination along the limb axis during these time windows has also enabled us to examine the pharmacokinetics of single-dose tamoxifen injections during pregnancy.
Nakamura
Eiichiro
E
Laboratory of Pathology, Center for Cancer Research, NCI, NIH, Bethesda, Maryland 20892, USA.
Nguyen
Minh-Thanh
MT
Mackem
Susan
S
D000818:Animals; D000831:Animals, Newborn; D001483:Base Sequence; D002356:Cartilage / Q000187:drug effects / Q000196:embryology* / Q000201:enzymology* / Q000254:growth & development; D020219:Chondrogenesis / Q000187:drug effects; D024043:Collagen Type II / Q000235:genetics; D017931:DNA Primers / Q000235:genetics; D005121:Extremities / Q000196:embryology* / Q000254:growth & development; D005260:Female; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects; D017930:Genes, Reporter; D005865:Gestational Age; D019426:Integrases / Q000008:administration & dosage / Q000378:metabolism*; D007700:Kinetics; D007763:Lac Operon; D051379:Mice; D008822:Mice, Transgenic; D011247:Pregnancy; D011995:Recombination, Genetic / Q000187:drug effects; D013629:Tamoxifen / Q000493:pharmacokinetics / Q000494:pharmacology*
C447413:Col2a1 protein, mouse; D024043:Collagen Type II; D017931:DNA Primers; D013629:Tamoxifen; C045073:Cre recombinase; D019426:Integrases