Lesions of Aryl-hydrocarbon Receptor–deficient Mice

• DOI: 10.1177/030098589703400609
• Publication Date: 2010-01-26T05:38:28Z
• Authors: P. M. Fernandez-S...; J. M. Ward; J. P. Sundberg; F. J. Gonzalez
• Keywords: Thymic involution

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