Differential gene dosage effects of Ad4BP/SF-1 on target tissue development.
Ad4BP/SF-1 (NR5A1) was identified as a key regulator of the hypothalamus-pituitary-gonadal and -adrenal axes. Loss-of-function studies revealed that Ad4BP/SF-1 is essential for the development of these tissues and spleen. Here, we generated transgenic mouse with BAC recombinants carrying a dual promoter and Tet-off system. These recombinants have a potential to express lacZ and Ad4BP/SF-1 in the tissues where endogenous Ad4BP/SF-1 is expressed. However, protein level of Ad4BP/SF-1 varied among the tissues of the transgenic mice and probably thereby the target tissues are affected differentially. The BAC-transgenic mice were applied to rescue Ad4BP/SF-1 KO mouse. Interestingly, the mice successfully rescued the gonad and spleen but failed to rescue the adrenal gland. This variation might be dependent on in part the protein expression levels among the tissues and in part on differential sensitivities to the gene dosage.
Fatchiyah
Division of Sex Differentiation, National Institute for Basic Biology, National Institutes of Natural Sciences, Okazaki 444-8787, Japan.
Zubair
Mohamad
M
Shima
Yuichi
Y
Oka
Sanae
S
Ishihara
Satoru
S
Fukui-Katoh
Yuko
Y
Morohashi
Ken-ichirou
K
D000311:Adrenal Glands / Q000254:growth & development*; D000818:Animals; D018628:Gene Dosage; D006066:Gonads / Q000254:growth & development*; D018398:Homeodomain Proteins / Q000235:genetics*; D007030:Hypothalamo-Hypophyseal System / Q000254:growth & development*; D051379:Mice; D018345:Mice, Knockout; D018160:Receptors, Cytoplasmic and Nuclear / Q000235:genetics*; D013154:Spleen / Q000254:growth & development; D054339:Steroidogenic Factor 1; D014157:Transcription Factors / Q000235:genetics*; D019076:Transgenes / Q000502:physiology
D018398:Homeodomain Proteins; D018160:Receptors, Cytoplasmic and Nuclear; D054339:Steroidogenic Factor 1; D014157:Transcription Factors