Comparative analyses of aryl hydrocarbon receptor structure and function in marine mammals
Comparative analyses of aryl hydrocarbon receptor structure and function in marine mammals
Date
2007-02
Authors
Lapseritis, Joy M.
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DOI
10.1575/1912/1761
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Keywords
Cetacea
Pollutants
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Abstract
Marine mammals possess high body burdens of persistent organic pollutants,
including PCBs and dioxin-like compounds (DLC). Chronic environmental or
dietary exposure to these chemicals can disrupt the function of reproductive and
immune systems, as well as cause developmental defects in laboratory animals.
The aryl hydrocarbon receptor (AHR) is a ligand-activated transcription factor,
mediating the expression of a suite of genes in response to exposure to DLC and
structurally related chemicals. Species-specific differences in AHR structure can
affect an organism’s susceptibility to the effects of DLC. The structures and
functions of several cetacean AHRs were investigated using in vitro molecular
cloning and biochemical techniques. Using a novel combination of remote
biopsy and molecular cloning methods, RNA was extracted from small
integument samples from living North Atlantic right whales to identify the cDNA
sequence for AHR and other genes of physiological importance. Biopsy-derived
RNA was found to be of higher quality than RNA extracted from stranded
cetaceans, and proved a good source for identifying cDNA sequences for
expressed genes. The molecular sequences, binding constants, and
transcriptional activities for North Atlantic right whale and humpback whale AHRs
cDNAs were determined using in vitro and cell culture methods. Whale AHRs
are capable of specifically binding dioxin and initiating transcription of reporter
genes. The properties of these AHRs were compared with those from other
mammalian species, including human, mouse, hamster, and guinea pig, and
other novel marine mammal AHRs, using biochemical, phylogenetic, and
homology modeling analyses. The relative binding affinities for some marine
mammal AHRs fall between those for the high-affinity mouse AHRb-1 and the
lower affinity human AHR. Species-specific variability in two regions of the AHR
ligand binding domain were identified as having the greatest potential impact on
AHR tertiary structure, yet does not sufficiently explain differences observed in
ligand binding assays. Additional studies are necessary to link exposure to
environmental contaminants with potential reproductive effects in marine
mammals, especially via interactions with steroid hormone receptor pathways.
Description
Submitted in partial fulfillment of the requirements for the degree of Doctor of Philosophy at the Massachusetts Institute of Technology and the Woods Hole Oceanographic Institution February 2007
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Citation
Lapseritis, J. M. (2007). Comparative analyses of aryl hydrocarbon receptor structure and function in marine mammals [Doctoral thesis, Massachusetts Institute of Technology and Woods Hole Oceanographic Institution]. Woods Hole Open Access Server. https://doi.org/10.1575/1912/1761