An Evolutionarily Conserved Role for the Aryl Hydrocarbon Receptor in the Regulation of Movement

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Using 43 strains from the BXD mouse reference population, we observed a 5-fold difference in spontaneous activity. QTL analysis indicated that ∼40% of this variance is due to the aryl hydrocarbon receptor (Ahr). Ahr is a conserved transcription factor found in nearly all multicellular organisms and implicated in a multitude of functions, ranging across development, liver metabolism, and neuronal health. This gene is highly variant in the BXDs, and strains with the low-active Ahr allele have significantly higher voluntary locomotion. This increase is also observed in independent mouse models, which have reduced Ahr activity, including in transgenic mice with humanized AHR. Furthermore, decreasing Ahr expression in C. elegans and Drosophila causes similar, robust increases in spontaneous movement. This link is independent of major environmental perturbations as well: BXD strains fed high fat diet long-term move only half as much as their chow-fed brethren, yet the effects of Ahr were consistent and equally strong in both dietary cohorts. While Ahr is a highly liganded transcription factor in mammals, these data indicate that modifications to its constitutive activity are sufficient to control movement. However, certain ligands may be able to specifically act on this phenotypic aspect of the gene.

Vyšlo v časopise: An Evolutionarily Conserved Role for the Aryl Hydrocarbon Receptor in the Regulation of Movement. PLoS Genet 10(9): e32767. doi:10.1371/journal.pgen.1004673
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1004673

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