Revealing Spleen Ad4BP/SF1 Knockout Mouse by BAC-Ad4BP-tTAZ Transgene

  • Fatchiyah 
  • M. Zubair
  • K. I. Morohashi
Part of the IFMBE Proceedings book series (IFMBE, volume 23)


The purpose of this study is addressed the function of Ad4BP/SF1 in developing spleen of Ad4BP/SF-1 KO mouse. I have modified the BAC-Ad4BP endogenous by homologous recombinant with modification cassette-containing tetracycline transactivator system and LacZ reporter genes to allow the expression of Ad4BP/SF1 in developing tissues and organ differentiation, regulate of Ad4BP/SF1 mechanism, and reveal the defect due to Ad4BP/SF1 deficiency. Recently studies, by immunihistochemistry of adult tissues showed that revealed coincident expressing between Ad4BP/SF-1 and lacZ, indicating the tTA system seemed to reproduces the endogenous expression of Ad4BP/SF-1, and thus likely to lacZ, Ad4BP/SF-1 in the BAC transgene was expected to be expressed in the corresponding tissues under the control of the bidirectional promoter. Interestingly, the BAC-Ad4BP-tTA transgenic mice were succeeded to up regulate the expression of Ad4BP/SF-1 at the protein level than wild type. And the fetal spleen of Tg(+);Ad4(+/+) was larger than that of the wild type, and expectedly the size of the spleen of Tg(+);Ad4(-/-) apparently recovered.


Ad4BP/SF-1 knockout mouse Spleen BAC transgenic homologous recombinant 


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  1. 1.
    Morohashi KI, Omura T. Ad4BP/SF-1, a transcription factor essential for the transcription of steroidogenic cytochrome P450 genes and for the establishment of the reproductive function. Faseb J 1996; 10: 1569–1577.Google Scholar
  2. 2.
    Parker KL, Schimmer BP. Steroidogenic factor 1: a key determinant of endocrine development and function. Endocr Rev 1997; 18: 361–377.CrossRefGoogle Scholar
  3. 3.
    Val P, Lefrancois-Martinez AM, Veyssiere G, Martinez A. SF-1 a key player in the development and differentiation of steroidogenic tissues. Nucl Recept 2003; 1–8.Google Scholar
  4. 4.
    Luo X, Ikeda Y, Parker KL. A cell-specific nuclear receptor is essential for adrenal and gonadal development and sexual differentiation. Cell 1994; 77: 481–490.CrossRefGoogle Scholar
  5. 5.
    Shinoda K, Lei H, Yoshii H, Nomura M, Nagano M, Shiba H, Sasaki H, Osawa Y, Ninomiya Y, Niwa O, et al. Developmental defects of the ventromedial hypothalamic nucleus and pituitary gonadotroph in the Ftz-F1 disrupted mice. Dev Dyn 1995; 204: 22–29.Google Scholar
  6. 6.
    Sadovsky Y, Crawford PA, Woodson KG, Polish JA, Clements MA, Tourtellotte LM, Simburger K, Milbrandt J. Mice deficient in the orphan receptor steroidogenic factor 1 lack adrenal glands and gonads but express P450 side chain-cleavage enzyme in the placenta and have normal embryonic serum levels of corticosteroids. Proc Natl Acad Sci USA 1995; 92: 10939–10943.CrossRefGoogle Scholar
  7. 7.
    Nomura M, Bartsch S, Nawata H, Omura T, Morohashi K. An E box element is required for the expression of the Ad4bp gene, a mammalian homologue of Ftz-f1 gene, which is essential for adrenal and gonadal development. J. Biol. Chem. 1995; 270: 7453–7461.CrossRefGoogle Scholar
  8. 8.
    Fatchiyah, M. Zubair, Y. Shima, S. Oka, S. Ishihara, Y. Fukui-Katoh, KI. Morohashi. Differential gene dosage effects of Ad4BP/SF-1 on target tissue development. ELSEVIER: Biochem. & Biophysical Com., 2006, 341: 1036–1045.CrossRefGoogle Scholar
  9. 9.
    Hogan B, Beddington, R, Costantini, F, Lacy, E. Manipulating the Mouse Embryo: A Laboratory Manual. NY: Cold Spring Harbor Laboratory Press; 1989Google Scholar
  10. 10.
    Sambrook J, Fritsch, EF, Maniatis, T. Molecular Cloning: A laboratory manual. NY: Cold Spring Harbor Laboratory Press; 1989.Google Scholar
  11. 11.
    Ikeda Y, Lala DS, Luo X, Kim E, Moisan MP, Parker KL. Characterization of the mouse FTZ-F1 gene, which encodes a key regulator of steroid hydroxylase gene expression. Mol Endocrinol 1993; 7: 852–860.CrossRefGoogle Scholar
  12. 12.
    Katoh-Fukui Y, Owaki A, Toyama Y, Kusaka M, Shinohara Y, Maekawa M, Toshimori K, Morohashi K. Mouse Polycomb M33 is required for splenic vascular and adrenal gland formation through regulating Ad4BP/SF1 expression. Blood 2005; 106: 1612–1620.CrossRefGoogle Scholar
  13. 13.
    Morohashi K, Tsuboi-Asai H, Matsushita S, Suda M, Nakashima M, Sasano H, Hataba Y, Li CL, Fukata J, Irie J, Watanabe T, Nagura H, Li E. Structural and functional abnormalities in the spleen of an mFtz-F1 gene-disrupted mouse. Blood 1999; 93:1586–1594.Google Scholar

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© International Federation of Medical and Biological Engineering 2009

Authors and Affiliations

  • Fatchiyah 
    • 1
  • M. Zubair
    • 2
  • K. I. Morohashi
    • 3
  1. 1.Dept. of Biology, School of ScienceBrawijaya UniversityMalangIndonesia
  2. 2.Dept. of Internal Medicine EndocrinologyUT South Western Medical CentreDallasUSA
  3. 3.Dept. of Molecular Biology, Graduate School of Medical SciencesKyushu UniversityFukuokaJapan

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