Lesions of Aryl-hydrocarbon Receptor–deficient Mice

1997 ◽  
Vol 34 (6) ◽  
pp. 605-614 ◽  
Author(s):  
P. M. Fernandez-Salguero ◽  
J. M. Ward ◽  
J. P. Sundberg ◽  
F. J. Gonzalez

We have analyzed the possible role of the aryl-hydrocarbon receptor (AHR) in the aging process of mice using a homozygous null mouse (Ahr-/-) line as a model. We studied 52 male and female Ahr-/- mice aged from 6-13 months. Forty-six percent died or were ill by 13 months of age. Ahr-/- mice developed age-related lesions in several organs, some of which were apparent after only 9 months of age. Cardiovascular alterations included cardiomyopathy (100%) with hypertrophy and focal fibrosis. Vascular hypertrophy and mild fibrosis were found in the portal areas of the liver (81%), and vascular hypertrophy and mineralization were common in the uterus (70%). Gastric hyperplasia that progressed with age into polyps was evident in the pylorus of 71% of the mice over 9 months of age. Ahr-/- mice had T-cell deficiency in their spleens but not in other lymphoid organs. The immune system deficiency described previously could be the origin for the rectal prolapse found in 48% of the null mice, associated with Helicobacter hepaticus infection. In the dorsal skin (53% incidence), severe, localized, interfollicular and follicular epidermal hyperplasia, with hyperkeratosis and acanthosis, and marked dermal fibrosis, associated with the presence of anagenic hair follicles, were also evident. None of these lesions were found in 42 control (Ahr +/+ or +/-) mice of similar ages. These observations suggest that the AHR protein, in the absence of an apparent exogenous (xenobiotic) ligand, plays an important role in physiology and homeostasis in major organs in mice, and further supports an evolutionary conserved role for this transcription factor.

2008 ◽  
Vol 28 (2-3) ◽  
pp. 61-67 ◽  
Author(s):  
R. Villalobos-Molina ◽  
F. G. Vázquez-Cuevas ◽  
J. J. López-Guerrero ◽  
M. C. Figueroa-García ◽  
I. A. Gallardo-Ortiz ◽  
...  

2021 ◽  
pp. 2100539
Author(s):  
Robert S. Chapkin ◽  
Laurie A. Davidson ◽  
Hyejin Park ◽  
Un‐Ho Jin ◽  
Yang‐Yi Fan ◽  
...  

Inflammation ◽  
2013 ◽  
Vol 37 (2) ◽  
pp. 387-395 ◽  
Author(s):  
Ping Wei ◽  
Guo-hua Hu ◽  
Hou-yong Kang ◽  
Hong-bing Yao ◽  
Wei Kou ◽  
...  

2020 ◽  
Author(s):  
Michelle M Lissner ◽  
Katherine Cumnock ◽  
Nicole M Davis ◽  
José G Vilches-Moure ◽  
Priyanka Basak ◽  
...  

2021 ◽  
Vol 22 (17) ◽  
pp. 9460
Author(s):  
Helmut Segner ◽  
Christyn Bailey ◽  
Carolina Tafalla ◽  
Jun Bo

The impact of anthropogenic contaminants on the immune system of fishes is an issue of growing concern. An important xenobiotic receptor that mediates effects of chemicals, such as halogenated aromatic hydrocarbons (HAHs) and polyaromatic hydrocarbons (PAHs), is the aryl hydrocarbon receptor (AhR). Fish toxicological research has focused on the role of this receptor in xenobiotic biotransformation as well as in causing developmental, cardiac, and reproductive toxicity. However, biomedical research has unraveled an important physiological role of the AhR in the immune system, what suggests that this receptor could be involved in immunotoxic effects of environmental contaminants. The aims of the present review are to critically discuss the available knowledge on (i) the expression and possible function of the AhR in the immune systems of teleost fishes; and (ii) the impact of AhR-activating xenobiotics on the immune systems of fish at the levels of immune gene expression, immune cell proliferation and immune cell function, immune pathology, and resistance to infectious disease. The existing information indicates that the AhR is expressed in the fish immune system, but currently, we have little understanding of its physiological role. Exposure to AhR-activating contaminants results in the modulation of numerous immune structural and functional parameters of fish. Despite the diversity of fish species studied and the experimental conditions investigated, the published findings rather uniformly point to immunosuppressive actions of xenobiotic AhR ligands in fish. These effects are often associated with increased disease susceptibility. The fact that fish populations from HAH- and PAH-contaminated environments suffer immune disturbances and elevated disease susceptibility highlights that the immunotoxic effects of AhR-activating xenobiotics bear environmental relevance.


2016 ◽  
Vol 23 (8) ◽  
pp. 960-975 ◽  
Author(s):  
Shunsuke Ito ◽  
Mizuko Osaka ◽  
Takeo Edamatsu ◽  
Yoshiharu Itoh ◽  
Masayuki Yoshida

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