title: The aryl hydrocarbon receptor (AhR) and its nuclear translocator (Arnt) are dispensable for normal mammary gland development but are required for fertility.
abstract: The aryl hydrocarbon receptor (AhR) and its nuclear translocator (Arnt) are transcription factors that play a role in the detection of and adaptation to environmental signals. AhR-null mice are viable but show impaired lactation. Deletion of the Arnt gene from the mouse genome results in embryonic lethality. To determine the role of Arnt in mammary development and function, we inactivated the Arnt gene in mammary epithelium using Cre-loxP recombination. Inactivation of the Arnt gene during pregnancy did not disrupt alveolar development or the ability of dams to nurse their litters. In contrast, dams in which the Arnt gene had been inactivated during puberty and in ovaries were subfertile, exhibited retarded mammary development, and impaired mammary function. To distinguish defects autonomous to mammary epithelium from indirect effects controlled by ovarian hormones, we transplanted Arnt-null and AhR-null mammary epithelium into wild-type mice and evaluated development after one pregnancy. Normal mammary structures were observed in the absence of Arnt and AhR, demonstrating that neither transcription factor is necessary for mammary development.
authors.affiliation: Laboratory of Genetics and Physiology, National Institute of Diabetes, Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892-0822, USA.
authors.forename: Fabienne
authors.initials: F
authors.lastname: Le Provost
authors.forename: Gregory
authors.initials: G
authors.lastname: Riedlinger
authors.forename: Sun
authors.initials: S
authors.lastname: Hee Yim
authors.forename: Jamie
authors.initials: J
authors.lastname: Benedict
authors.forename: Frank J
authors.initials: FJ
authors.lastname: Gonzalez
authors.forename: Jodi
authors.initials: J
authors.lastname: Flaws
authors.forename: Lothar
authors.initials: L
authors.lastname: Hennighausen
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D051784:Aryl Hydrocarbon Receptor Nuclear Translocator; D004268:DNA-Binding Proteins; D005260:Female; D005298:Fertility / Q000235:genetics*; D005786:Gene Expression Regulation; D019426:Integrases / Q000235:genetics; D008321:Mammary Glands, Animal / Q000254:growth & development* / Q000378:metabolism / Q000648:ultrastructure; D051379:Mice; D008822:Mice, Transgenic; D009928:Organ Specificity; D010053:Ovary / Q000254:growth & development / Q000378:metabolism; D018336:Receptors, Aryl Hydrocarbon / Q000235:genetics / Q000378:metabolism*; D014157:Transcription Factors / Q000378:metabolism*; D014764:Viral Proteins / Q000235:genetics
chemical_list: C497397:Arnt protein, mouse; D004268:DNA-Binding Proteins; D018336:Receptors, Aryl Hydrocarbon; D014157:Transcription Factors; D014764:Viral Proteins; D051784:Aryl Hydrocarbon Receptor Nuclear Translocator; C045073:Cre recombinase; D019426:Integrases