PMID- 17035482
OWN - NLM
STAT- MEDLINE
DCOM- 20070205
LR  - 20161124
IS  - 1096-6080 (Print)
IS  - 1096-0929 (Linking)
VI  - 95
IP  - 1
DP  - 2007 Jan
TI  - TCDD-induced alterations in gene expression profiles of the developing mouse paw 
      do not influence morphological differentiation of this potential target tissue.
PG  - 240-8
AB  - The aryl-hydrocarbon receptor (AhR) is a ligand-dependent transcription factor 
      that mediates the toxicity of certain halogenated aromatic hydrocarbons including 
      2,3,7,8-tetra-chlorodibenzo-p-dioxin (TCDD). These compounds are potent 
      developmental toxicants that can alter gene expression and disrupt processes of 
      proliferation and differentiation. It has not yet been determined which tissues 
      during development are most sensitive to these compounds, nor which genes are 
      directly associated with the toxicities. We developed a transgenic (TG) mouse 
      model to delineate the temporal and spatial context of transcriptionally active 
      AhR by utilizing a dioxin responsive element-linked LacZ reporter system. The 
      present study focuses on the pattern of TCDD-induced transgene expression 
      localized to the footpad and digits of the paws between gestational days (GD) 13 
      and 18. Paw morphology was evaluated at several developmental stages following 
      TCDD exposure. Gene expression profiles acquired by microarray technology were 
      evaluated in the paws of fetuses exposed at GD 14.5. The results showed that TCDD 
      exposure in utero induced LacZ expression in the developing paws. This expression 
      appeared to be localized to the mesenchymal cell layer. Gross morphological 
      changes were not observed in the paws prior to or after birth following TCDD 
      exposure in utero. However, significant alterations in gene expression profiles 
      in the developing paws were observed at 24 h following TCDD exposure in utero. 
      These results indicate that the developing paw is a target tissue of TCDD in 
      terms of altered gene expression, further validating the use of this AhR 
      responsive reporter gene TG mouse model in studying AhR ligand-mediated 
      responsiveness. However, the linkage of these changes to detectable biological 
      outcomes in the paw remains unclear.
FAU - Bemis, Jeffrey C
AU  - Bemis JC
AD  - Department of Environmental Medicine, Rochester, New York 14642, USA.
FAU - Alejandro, Napoleon F
AU  - Alejandro NF
FAU - Nazarenko, Daniel A
AU  - Nazarenko DA
FAU - Brooks, Andrew I
AU  - Brooks AI
FAU - Baggs, Raymond B
AU  - Baggs RB
FAU - Gasiewicz, Thomas A
AU  - Gasiewicz TA
LA  - eng
GR  - ES01247/ES/NIEHS NIH HHS/United States
GR  - ES07026/ES/NIEHS NIH HHS/United States
GR  - ES09430/ES/NIEHS NIH HHS/United States
GR  - ES09702/ES/NIEHS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20061011
PL  - United States
TA  - Toxicol Sci
JT  - Toxicological sciences : an official journal of the Society of Toxicology
JID - 9805461
RN  - 0 (Carcinogens, Environmental)
RN  - 0 (Polychlorinated Dibenzodioxins)
RN  - 0 (RNA, Messenger)
RN  - 0 (Receptors, Aryl Hydrocarbon)
SB  - IM
MH  - Animals
MH  - Carcinogens, Environmental/*toxicity
MH  - Cell Differentiation/drug effects
MH  - Embryonic Development/*drug effects
MH  - Female
MH  - Forelimb/*embryology
MH  - *Gene Expression Profiling
MH  - Gene Expression Regulation, Developmental/*drug effects
MH  - Genes, Reporter
MH  - Gestational Age
MH  - Lac Operon
MH  - Maternal Exposure
MH  - Mesoderm/cytology/*drug effects/metabolism
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Transgenic
MH  - Oligonucleotide Array Sequence Analysis
MH  - Polychlorinated Dibenzodioxins/*toxicity
MH  - Pregnancy
MH  - RNA, Messenger/metabolism
MH  - Receptors, Aryl Hydrocarbon/*agonists/genetics/metabolism
MH  - Reproducibility of Results
MH  - Response Elements/drug effects/genetics
MH  - Reverse Transcriptase Polymerase Chain Reaction
EDAT- 2006/10/13 09:00
MHDA- 2007/02/06 09:00
CRDT- 2006/10/13 09:00
PHST- 2006/10/13 09:00 [pubmed]
PHST- 2007/02/06 09:00 [medline]
PHST- 2006/10/13 09:00 [entrez]
AID - kfl132 [pii]
AID - 10.1093/toxsci/kfl132 [doi]
PST - ppublish
SO  - Toxicol Sci. 2007 Jan;95(1):240-8. doi: 10.1093/toxsci/kfl132. Epub 2006 Oct 11.