Tissue-selective knockouts of steroid receptors: a novel paradigm in the study of steroid action.
The use of tissue-selective rather than ubiquitous knockouts of steroid receptors allows a more refined study of the mechanism of steroid action in defined target tissues and circumvents problems such as early lethality or major developmental defects precluding studies in affected organs. In this chapter, we describe the main steps involved in the development of tissue-selective steroid receptor knockouts by Cre/loxP technology. Problems in the development of a mouse strain with a floxed receptor allele, the selection of a suitable Cre expressing mouse strain, the generation of cell-selective knockouts by crossbreeding of the mentioned mouse strains, and the control of appropriate receptor inactivation are discussed taking the generation of mice with a Sertoli cell-selective ablation of the androgen receptor as an example.
De Gendt
Karel
K
Laboratory for Experimental Medicine and Endocrinology, Catholic University of Leuven, Leuven, Belgium.
Verhoeven
Guido
G
D000818:Animals; D001483:Base Sequence; D053595:Embryonic Stem Cells / Q000166:cytology / Q000502:physiology; D005260:Female; D005822:Genetic Vectors / Q000235:genetics / Q000378:metabolism; D019426:Integrases / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008969:Molecular Sequence Data; D011944:Receptors, Androgen / Q000235:genetics / Q000378:metabolism; D011987:Receptors, Steroid / Q000235:genetics / Q000378:metabolism*; D011995:Recombination, Genetic
D011944:Receptors, Androgen; D011987:Receptors, Steroid; C045073:Cre recombinase; D019426:Integrases