Genetic dissection of corticosteroid receptor function in mice.
Functional genomic technologies, including artificial chromosome-based transgenesis and conditional gene targeting, allowed us to generate mouse models harboring genes with loss-of-function mutations, gain-of-function mutations, spatially and/or temporally restricted mutations, tissue-specific mutations, and function-selective mutations. This kind of "allelic series" for corticosteroid receptors in mouse models provides a very useful resource for the molecular understanding of corticosteroid function in vivo. These models will also support the identification of steroid receptor target genes in order to define a steroid signaling cascade in molecular terms. They provide opportunities for the identification of compounds that regulate steroid receptors in a tissue-specific and function-selective manner. For example, selective glucocorticoid receptor modulators preventing receptor dimerization and DNA binding can be expected to reduce osteoporotic and/or diabetogenic side effects, but to display partial or full anti-inflammatory potential. Thus, these mouse models will help to evaluate distinct steroid receptor functions for therapeutic intervention.
Wintermantel
T M
TM
Molecular Biology of the Cell I, German Cancer Research Center, Im Neuenheimer Feld 280, 69120 Heidelberg, Germany.
Berger
S
S
Greiner
E F
EF
Schütz
G
G
D000818:Animals; D003920:Diabetes Mellitus / Q000235:genetics / Q000503:physiopathology; D019281:Dimerization; D005786:Gene Expression Regulation / Q000235:genetics / Q000502:physiology; D051379:Mice; D018345:Mice, Knockout; D009154:Mutation; D010024:Osteoporosis / Q000235:genetics / Q000503:physiopathology; D011965:Receptors, Glucocorticoid / Q000235:genetics* / Q000502:physiology; D015398:Signal Transduction / Q000235:genetics / Q000502:physiology; D014157:Transcription Factors / Q000235:genetics* / Q000502:physiology
D011965:Receptors, Glucocorticoid; D014157:Transcription Factors