The DOI matches its Crossref record; 38 of the 38 references it cites were found in a registry or an index.
Genomic actions of the androgen receptor are required for normal male sexual differentiation in a mouse model
Open accessAbstract
Androgens mediate their effects in target cells via the androgen receptor (AR), which acts predominantly as a ligand-dependent transcription factor. In addition, androgens induce rapid activation of second messenger signal transduction cascades, and this is thought to occur via non-genomic mechanisms. We have used the Cre/loxP system to generate an AR knockout (ARKO) mouse targeting exon 3, which encodes the second zinc finger of the DNA-binding domain. To generate universal ARKO mice, floxed AR mice were mated with CMV-Cre mice, which express Cre recombinase ubiquitously. Deletion of the floxed allele in our mice does not disrupt the reading frame, and has been designed so that the mutant AR can bind ligand but not target genes. ARKO males displayed a complete androgen insensitivity phenotype, with female external genitalia and a reduction in body weight compared with wild-type males (P < 0.001). Testes of ARKO males were smaller than control males (P < 0.0001) and were located intra-abdominally. We have demonstrated that genotypically XY mice lacking the second zinc finger of the AR have a female phenotype, and we conclude that the genomic actions of the AR (mediated by DNA binding) are indispensable for normal male sexual differentiation.
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“The differences in the fat phenotype of these ARKO models may be attributed to the differences in the genetic background of the mice 126 as well as the region of the AR targeted for deletion”
From The role of the androgen receptor in the pathogenesis of obesity and its utility as a target for obesity treatments (2022) · cites this paper as [145]
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DNA binding of the glucocorticoid receptor is not essential for survival
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A Sertoli cell-selective knockout of the androgen receptor causes spermatogenic arrest in meiosis
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Androgen Receptor Structure, Function and Biology: From Bench to Bedside.
(2016) · Europe PMC (PubMed Central) · Cited by 623
Self-citationLow Testosterone in Men with Type 2 Diabetes: Significance and Treatment
Grossmann, M. (2011) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2011-0118 · Cited by 350
Genetic and molecular insights into the development and evolution of sexual dimorphism
Williams, T. M., & Carroll, S. B. (2009) · Nature Reviews Genetics · doi:10.1038/nrg2687 · Cited by 347
Sex Steroid Actions in Male Bone
Vanderschueren, D., Laurent, M. R., Claessens, F., Gielen, E., Lagerquist, M. K., Vandenput, L., Börjesson, A. E., & Ohlsson, C. (2014) · Endocrine Reviews · doi:10.1210/er.2014-1024 · Cited by 327
The Androgen Receptor in Health and Disease
Μatsumoto, T., Sakari, M., Okada, M., Yokoyama, A., Takahashi, S., Kouzmenko, A., & Kato, S. (2012) · Annual Review of Physiology · doi:10.1146/annurev-physiol-030212-183656 · Cited by 275
Metadata
- Authors
- Notini, A. J., Davey, R. A., McManus, J. F., Bate, K. L., & Zajac, J. D.
- Affiliations
- The University of Melbourne (AU)
- ORCID
- Venue
- Journal of Molecular Endocrinology
- Publisher
- Bioscientifica
- Published
- 2005-12-01
- Volume
- 35
- Issue
- 3
- Pages
- 547-555
- ISSN
- 0952-5041 (ISSN-L)
- 1479-6813
- OpenAlex
- W2104537307
- Cited by
- 145
- References
- 37
- Citations by year
- 2025: 2 · 2024: 8 · 2023: 5 · 2022: 3 · 2021: 5 · 2020: 7 · 2019: 4 · 2018: 5 · 2017: 8 · 2016: 10 · 2015: 12 · 2014: 18 · 2013: 9 · 2012: 10
- FWCI
- 2.24
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Molecular Endocrinology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Eli Lilly and Company
- Cass Foundation
- Eli Lilly Australia
- Medical Research Council
- National Health and Medical Research Council
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Sexual Differentiation and Disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic and Clinical Aspects of Sex Determination and Chromosomal Abnormalities
- Health Sciences › Medicine › Reproductive Medicine › Sperm and Testicular Function
- Keywords
- androgen receptor, male sexual differentiation, androgen insensitivity syndrome, DNA-binding domain, Cre-loxP system, second messenger signaling, testicular development, external genitalia, XY females
- MeSH terms
- Animals, Base Sequence, Binding Sites, Female, Male, Mice, Inbred C57BL, Mice, Transgenic, Phenotype, Pregnancy, Receptors, Androgen, Sex Differentiation, Androgen-Insensitivity Syndrome, Zinc Fingers, Genome, DNA, Complementary, Mice, Knockout, Gene Targeting, Mice
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