Title: A role for selective androgen response elements in the development of the epididymis and the androgen control of the 5α reductase II gene
Authors: Kerkhofs, Stefanie ×
Dubois, Vanessa
De Gendt, Karel
Helsen, Christine
Clinckemalie, Liesbeth
Spans, Lien
Schuit, Frans
Boonen, Steven
Vanderschueren, Dirk
Saunders, Philippa T K
Verhoeven, Guido
Claessens, Frank #
Issue Date: Oct-2012
Publisher: The Federation of American Societies for Experimental Biology
Series Title: FASEB Journal vol:26 issue:10 pages:4360-4372
Abstract: The androgen receptor (AR) recognizes two types of DNA elements that are dimers of 5'-AGAACA-3'-like hexamers, either organized as inverted or direct repeats. We developed a mouse model [(specificity affecting AR knock-in (SPARKI)] in which the AR DNA-binding domain was mutated such that it lost binding to direct repeats but not to inverted elements. The impaired fertility of the male SPARKI mice correlates with the reduced motility of the spermatozoa, a characteristic that is developed during transit through the epididymis. Comparative transcriptome analyses revealed that the expression of 39 genes is changed in SPARKI epididymis. Remarkably, the expression of the steroid 5α-reductase type II (Srd5α2) gene, which metabolizes testosterone into the more potent dihydrotestosterone, is reduced 4-fold in SPARKI vs. wild type. The comparison of the SPARKI phenotype with that of Srd5α2-knockout mice shows, however, that the reduced Srd5α2 expression cannot explain all defects of the SPARKI epididymis. Moreover, we describe three new selective androgen response elements (AREs), which control the androgen responsiveness of the Srd5α2 gene. We conclude that the SPARKI model can be considered a knockout model for AR functioning via selective AREs and that this has a dramatic effect on sperm maturation in the epididymis.-Kerkhofs, S., Dubois, V., De Gendt, K., Helsen, C., Clinckemalie, L., Spans, L., Schuit, F., Boonen, S., Vanderschueren, D., Saunders, P. T. K., Verhoeven, G., Claessens, F. A role for selective androgen response elements in the development of the epididymis and the androgen control of the 5α reductase II gene.
ISSN: 0892-6638
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Gene Expression Unit
Laboratory of Molecular Endocrinology
Department of Oncology - miscellaneous
Clinical and Experimental Endocrinology
× corresponding author
# (joint) last author

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