Juntendo University, Tokyo, established in 1838.

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  4. Yoshihiko Araki M.D., D.Med.Sci.

Institute for Environmental and Gender-Specific Medicine

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Yoshihiko Araki M.D., D.Med.Sci.

M.D.: Yamagata University (1983)
D.Med.Sci.: Yamagata University (1987)
Postdoctral: Case Western Reserve University, Vanderbilt University

Academic appointments:

Assistant Professor, Department of Obstetrics & Gynecology
Yamagata University School of Medicine
Associate Professor, Department of Immunology & Parasitology,
Yamagata University School of Medicine
Research Associate Professor, Vanderbilt University School of Medicine,
Department of Obstetrics & Gynecology
Associate Professor, Yamagata University School of Medicine,
Department of Immunology & Parasitology
Associate Professor, Juntendo University Graduate School of Medicine,
Institute for Environmental & Gender-specific Medicine
Adjunct Associate Professor, Juntendo University Graduate School of Medicine,
Department of Obstetrics & Gynecology
Deputy Director, Juntendo University Graduate School of Medicine, Institute for Environmental & Gender-specific Medicine
Visiting Professor, Division of Microbiology, Department of Pathology and Microbiology, Nihon University School of Medicine

Society membership:

International Society for Immunology of Reproduction
Society for the Study of Reproduction
Japan Society of Obstetrics and Gynecology
Japan Society for Immunology of Reproduction
American Society of Andrology
Japan Society for Immunology
The Society for Reproduction and Development
Japanese Society for the History of Medicine

Reviewer (Since 1992 to date):

Biology of Reproduction, Human Reproduction, Zygote, Reproduction, Molecular Reproduction & Development, Immunobiology, FEBS Journal (European Journal of Biochemistry), Journal of Andrology, Journal of Biosciences, Journal of Molecular Histology, Cancer Letter, Journal of Molecular Endocrinology, Molecular Biology Reports, Reproductive BioMedicine Online, Environmental Health and Preventive Medicine, The Open Medical Informatics Journal, British Journal of Cancer, International Journal of Developmental Biology, International Journal of Food Sciences & Nutrition, Gene, International Journal of Andrology, Journal of Cell Science, Clinical & Experimental Immunology, Immunology, Journal of Reproductive Immunology, Annals of Medicine, Journal of Obstetrics and Gynaecology Research, The Open Reproductive Science Journal, Molecular Human Reproduction, Biochemistry Research International, International Journal of Biological Markers, Scientific Reports, PLOS ONE, Livestock Science, Journal of the Japanese Society for the History of Medicine, The Protein Journal, Studies in Natural Products Chemistry -Bioactive Natural Products- (Ed:Atta-ur-Rahman, Elsevier Science), Cytokine, American Journal of Reproductive Immunology, Reproduction Fertility and Development, Experimental Dermatology, Molecular & Cellular Proteomics, Medical Hypotheses

Editorial Board:

The Open Reproductive Science Journal (2007-2015)
Scientific Reports (2014 to date)

Office Address:

Institute for Environmental & Gender-specific Medicine,
Juntendo University Graduate School of Medicine
2-1-1 Tomioka, Urayasu-City 279-0021, Japan
Tel: 81-47-353-3171
Fax: 81-47-353-3178
E-mail: yaraki@juntendo.ac.jp


Hiroshi Yoshitake, M.D., Ph.D. Assistant Professor (part time)
Kenji Yamatoya, Ph.D. Assistant Professor
Isei Ninomiya, M.D. Graduate School Student (Dept. of Opthalmol)
Masaru Kurosawa Ph.D. Research Associate
Ryota Kosuge, Research Assistant

Associate members:

Mitsuo Ohkubo M.D., Ph.D. Associate Professor (Dept. of Transfusion Medicine and Stem Cell Regulation)
Mitsuaki Yanagida Ph.D. Associate Professor (Inst. for Environment. & Gender-specific Med.)

Research Keywords:

gametegenesis; fertilization; implantation, oviduct, GPI-anchored protein

Research Specialty:

We are interested in control mechanism of gametegenesis, sperm-egg interaction, and implantation,i.e. , fundamental biological process required for sexual reproduction.

Research Description:

Molecular mechanism of mammalian reproduction

  The research in our laboratory focuses on two areas of mammalian reproductive biology. First, our work has been directed toward understanding the molecular mechanism(s) of gametogenesis, especially sex difference during sperm/oogenesis. We identified a testicular protein (TEX101) predominantly expressed on the cell surface of spermatocytes and spermatids but not on the surface of Sertoli cells or interstitial cells, including Leydig cells, in adult mice. In developing testis, TEX101 is present on prospermatogonia in the immature seminiferous cords from 14 days post-coitus until 8 days post-partum. Thereafter, prospermatogonia arrange around the basal membranes of the seminiferous tubules and spermatogenesis is initiated. At this stage, TEX101 disappears from spermatogonia and is instead detected in spermatocytes and spermatids. Interestingly, sexually dimorphic expression of TEX101 is observed in developing gonadal tissues. For example, oogonia temporarily express TEX101 during the fetal stage, but the molecule is not detected in the sexually mature ovary. Using this molecule as a specific marker of the germ cell, we are currently investigating molecular regulation of male/female-specific gametegenesis as well as fertilization/implantation.
  A second area of interest is the microenvironment of the fertilization process in vivo. The mammalian fertilization process takes place in a complex microenvironment within the female genital tract. Although normal fertilization and pre-implantation development in vitro are possible without factors supplied from female genital tract, the significance of the microenvironment is no doubt essential for fertilization and early embryonic development. To evaluate physiological significance of the environment surrounded zygote in vivo, we are currently focused on immunological signal transduction during fertilization and early development at the site of fertilization, or oviduct.
  Our long-term goal would be to understand what is an essential difference between male and female. The information gained from studies described above will provide the framework to compare some aspects of male/female. Since most of living organizations are recognized as having ability for sexual reproduction, only hints to understand gender-specificity may exist as to how gametogenesis is regulated and what molecular mechanisms underlie this basic biological response.

Articles in the refereed journals

(Selected since 2006 to date: *Correspondence; Present or past group members of the research group)
  1. Araki Y*. Commentary on a "Strategy to develop clinical peptide biomarkers for more accurate evaluation of the pathophysiological status of hypertensive disorders of pregnancy". Clinics Mother Child Health, 2020 (in press)
  2. Okubo M*, Furuta Y, Nakamura Y, Osawa T, Tada N, Sawada T, Yamatoya K, Sekiguchi Y, Araki Y, Miyake K, Noguchi M, Komatsu N, Ohsaka A. A threshold for optimal administration of plerixafor in autologous peripheral blood stem cell collections through CD34+ cell monitoring based on the experience from two Japanese university hospitals. Ther.Apher.Dial. 2020 (published Online on Dec. 16, 2020). https://doi.org/10.1111/1744-9987.13614
  3. Araki Y*, Yoshitake H, Yamatoya K, Fujiwara H. An overview of sex and reproductive immunity from an evolutionary/anthropological perspective. Immunol.Med. Published online: 11 Oct 2020. https://doi.org/10.1080/25785826.2020.1831219
  4. Yoshitake H, Araki Y.* Role of the glycosylphosphatidylinositol-anchored protein TEX101, and its related molecules in spermatogenesis. Int.J.Mol.Sci. 21, 6628, 2020. doi:10.3390/ijms21186628
  5. Fujiwara H*, Ono M, Sato Y, Imakawa K, Iizuka T, Kagami K, Fujiwara T, Horie A, Tani H, Hattori A, Daikoku T, Araki Y. Promoting roles of embryonic signals in embryo implantation and placentation in cooperation with endocrine and immune systems. Int.J.Mol.Sci. 21, 1885, 2020. doi:10.3390/ijms21051885
  6. Yamatoya K*, Kousaka M, Ito C, Nakata K, Hatano M, Araki Y, Toshimori K. Cleavage of SPACA1 regulates assembly of sperm-egg membrane fusion machinery in mature spermatozoa. Biol.Reprod. 102:750-757, 2020. doi:10.1093/biolre/ioz223
  7. Araki Y*, Yanagida M. Hypertensive disorders of pregnancy: strategy to develop clinical peptide biomarkers for more accurate evaluation of the pathophysiological status of this syndrome. In: Adv Clin Chem (Makowski GS. ed.) Vol. 94, pp1-30, Elsevier, London, UK, 2020. (Cover Image: https://doi.org/10.1016/bs.acc.2019.07.007)
  8. Tanaka T, Tanaka K, Nakano T, Hozumi Y, Yanagida M, Araki Y, Iwazaki K, Takagi M, Goto K*. Knockdown of DEAD-box RNA helicase DDX5 selectively attenuates serine 311 phosphorylation of NF-κB p65 subunit and expression level of anti-apoptotic factor Bcl-2. Cell. Signal. 65:109428, 2020. https://doi.org/10.1016/j.cellsig.2019.109428
  9. Oda-Sakurai R, Yoshitake H, Miura Y, Kazuno S. Ueno T, Hasegawa A, Yamatoya K, Takamori K, Itakura A, Fujiwara H, Takeda S, Araki Y*. NUP62: the target of an anti-sperm auto-monoclonal antibody during testicular development. Reproduction 158:503-516, 2019. doi: https://doi.org/10.1530/REP-19-0333 
  10. Yanagida M, Hamamura K, Takamori K, Araki Y*. The simultaneous quantification of candidate serum biomarker peptides for hypertensive disorders of pregnancy. Ann.Clin.Biochem. 56:457-465, 2019. doi: 10.1177/0004563219839084
  11. Fujiwara H*, Matsumoto H, Sato Y, Horie A, Ono M, Nakamura M, Mizumoto Y, Kagami K, Fujiwara T, Hattori A, Maida Y, Daikoku T, Imakawa K, Araki Y.  Factors regulating human extravillous trophoblast invasion: Chemokine-peptidase and CD9-integrin systems.  Cur.Pharm.Biotech. 19: 764-770, 2018. doi: 10.2174/138920101910181112114656
  12. Hamamura K, Yanagida M, Ishikawa H, Banzai M, Yoshitake H, Nonaka D, Tanaka K, Sakuraba M, Miyakuni Y, Takamori K, Nojima M, Yoshida K, Fujiwara H, Takeda S, Araki Y*.  Quantitative measurement of a candidate serum biomarker peptide derived from α2-HS-glycoprotein, and a preliminary trial of multi-dimensional peptide analysis in women with pregnancy induced hypertension. Ann.Clin.Biochem. 55:287-295, 2018. doi: 10.1177/0004563217717748
  13. Suginami K, Sato Y, Horie A, Matsumoto H, Tani H, Mizumoto Y, Matsuoka A, Kyo S, Araki Y, Konishi I., Fujiwara H*.  Platelet-derived microparticles and soluble factors differentially regulate human endometrial epithelial cell movement. Am.J.Reprod.Immunol. 77:e12641, 2017. doi: 10.1111/aji.12641.
  14. Suginami K, Sato Y, Horie A, Matsumoto H, Kyo S, Araki Y, Konishi I, Fujiwara H*. Platelets are a possible regulator of human endometrial re-epithelialization during menstruation. Am.J.Reprod.Immunol. 77:e12609, 2017. doi: 10.1111/aji.12609.
  15. Matsumoto H, Sato Y, Horie A, Suginami K, Tani H, Hattori A, Araki Y, Kagami K, Konishi I, Fujiwara H*. CD9 suppresses human extravillous trophoblast invasion. Placenta 47:105-112, 2016. doi: 10.1016/j.placenta.2016.09.014
  16. Yoshitake H, Oda R, Yanagida M, Kawasaki Y, Sakuraba M, Takamori K, Hasegawa A, Fujiwara H, Araki Y*.  Identification of an anti-sperm auto-monoclonal antibody (Ts4)-recognized molecule in the mouse sperm acrosomal region and its inhibitory effects on fertilization in vitro. J.Reprod.Immunol. 115: 6-13, 2016. doi:10.1016/j.jri.2016.04.001
  17. Endo S, Yoshitake H, Tsukamoto H, Matsuura H, Kato K, Sakuraba M, Takamori K, Fujiwara H, Takeda S, Araki Y.* TEX101, a glycoprotein essential for sperm fertility, is required for stable expression of Ly6k on testicular germ cells.  Sci.Rep. 6: 23616, 2016. doi: 10.1038/srep23616.
  18. Fujiwara H*, Araki Y, Sato Y, Takakura M, Nakamura M, Mizumoto Y, Horie A, Kanzaki H, Mori T.  Role of circulating blood cells in maternal tissue remodeling and embryo-maternal cross talk.In: Uterine Endometrial Function (Kanzaki H. ed.) pp. 49-60, Springer Japan, Tokyo, Japan, 2016.
  19. Hamamura K, Nonaka D., Ishikawa H., Banzai M., Yoshitake H, Yanagida M, Nojima M, Yoshida K, Takamori K, Asada K, Lee L-J, Tanaka K, Takeda S, Araki Y*.  Simple quantitation for potential serum disease biomarker peptides, primarily identified by a peptidomics approach in the serum with hypertensive disorders of pregnancy.  Ann.Clin.Biochem. 53: 85-96, 2016. doi:10.1177/0004563215583697.
  20. Fujiwara H*, Araki Y, Imakawa K, Saito S, Daikoku T, Shigeta M, Kanzaki H, Mori T.  Dual positive regulation of embryo implantation by endocrine and immune systems - Step-by-Step maternal recognition of the developing embryo.  Am.J.Reprod.Immunol. 75: 281-289, 2016.  doi:10.1111/aji.12478.
  21. Bodogai M, Moritoh K, Lee-Chang C, Hollander MC, Sherman-Baust C, Wersto R, Araki Y., Miyoshi I, Yang L, Trinchieri G, Biragyn A*.  Regulatory and pro-metastatic function of myeloid-derived suppressive cells requires education from tumor-associated B cells.  Cancer Res. 75: 3456-3465, 2015, doi: 10.1158/0008-5472.CAN-14-3077.
  22. Fujiwara H*, Araki Y, Saito S, Imakawa K, Kyo S, Shigeta M, Shiotani M, Horie A, Mori T.  A novel concept of Fundus-Ovary-Salpinx-Para-Aorta implantation promoting unit during human embryo implantation.  In: New Discoveries of Embryology (Wu B. ed.)  pp77-95, InTech Open Access Publisher, Rijeka, Croatia. 2015. DOI:10.5772/60634
  23. Yoshitake H, Hashii N, Kawasaki N, Endo S, Takamori K, Hasegawa A, Fujiwara H, Araki Y*. Chemical characterization of N-linked oligosaccharide as the antigen epitope recognized by an anti-sperm auto-monoclonal antibody, Ts4. PLOS ONE 10: e0133784, 2015, doi: 10.1371/journal.pone.0133784
  24. Kantake M*, Yoshitake H, Ishikawa H, Araki Y, Shimizu T.  Postnatal epigenetic modification of glucocorticoid receptor gene in preterm infants: a prospective cohort study.  BMJ Open 4: e005318. doi:10.1136/bmjopen-2014-005318, 2014.
  25. Sherman-Baust CA, Kuhn E, Valle BL, Shih I-M, Kurman RJ, Wang TL, Amano T, Ko MHS, Miyoshi I, Araki Y, Lehrmann E, Zhang Y, Becker KG, Morin PJ.  A genetically engineered ovarian cancer mouse model based on fallopian tube transformation mimics human high-grade serous carcinoma development.  J Pathol. 233: 228-237, 2014.
  26. Araki Y*, Nonaka D, Hamamura K, Yanagida M, Ishikawa H, Banzai M, Maruyama M, Endo S, Tajima A, Lee L-J, Nojima M, Takamori K, Yoshida K, Takeda S, Tanaka K.  Clinical peptidomic analysis by a one-step direct transfer technology: Its potential utility for monitoring of pathophysiological status in female reproductive system disorders.  J. Obstet. Gynecol. Res. 39:1440-1448, 2013.
  27. Fujihara Y, Tokuhiro K, Muro Y, Kondoh G, Araki Y, Ikawa M, Okabe M*.  Expression of TEX101, regulated by ACE, is essential for the production of fertile mouse spermatozoa.  Proc.Natl.Acad.Sci. U.S.A. 110:8111-8116, 2013.
  28. Honda M*, Asai T, Oku N, Araki Y, Tanaka M, Ebihara N.  Liposomes and nanotechnology in drug development: Focus on ocular targets.  Int. J. Nanomed. 8; 495-504, 2013.
  29. Fujiwara H*, Nishioka Y, Matsumoto H, Suginami K, Horie A, Tani H, Matsumura N, Baba T, Sato Y, Araki Y, Konishi I.  Eph-ephrin A system regulates human choriocarcinoma-derived JEG-3 cell invasion.  Int.J.Gynecol.Cancer  23:576-582, 2013.
  30. Yoshitake H, Yokoi H, Ishikawa H, Maruyama M, Endo S, Nojima M, Yoshida K, Yoshikawa H, Suzuki F, Takamori K, Fujiwara H, Araki Y*.  Overexpression of TEX101, a potential novel cancer marker, in head and neck squamous cell carcinoma. Cancer Biomark. 12:141-148, 2012/2013.
  31. Okada M, Hozumi Y, Tanaka T, Suzuki Y, Yanagida M, Araki Y, Evangelisti C, Yagisawa H, Matthew K, Topham MK, Martelli AM, Goto K*.  DGKζ is degraded through the cytoplasmic ubiquitin-proteasome system under excitotoxic conditions, which causes neuronal apoptosis because of aberrant cell cycle reentry.  Cell. Signal.  24:1573-1582, 2012.
  32. Fujiwara H*, Sato Y, Ideta A, Aoyagi Y, Araki Y, Imakawa K.  Immune regulation of human embryo implantation by circulating blood cells.  In: The Human Embryo (Yamada S., Takakuwa T. eds), P61-72, InTech Open Access Publisher, Rijeka, Croatia. 2012.
  33. Okada M, Hozumi Y, Iwazaki K, Misaki K, Yanagida M, Araki Y, Watanabe T, Yagisawa H, Topham MK, Kaibuchi K, Goto K*.  DGKζ is involved in LPS-activated phagocytosis through IQGAP1/Rac1 pathway.  Biochem.Biophys.Res.Commun. 420:479-484., 2012.
  34. Takizawa T, Ishikawa T, Kosuge T, Mizuguchi Y, Sato Y, Koji T, Araki Y, Takizawa T*.  Gene suppression of mouse testis in vivo using small interfering RNA derived from plasmid vectors.  Acta Histochem.Cytochem. 45;77-81, 2012.
  35. Yoshitake H, Yanagida M, Maruyama M, Takamori K, Hasegawa A, Araki Y*. Molecular characterization and expression of dipeptidase 3, a testis-specific membrane bound dipeptidase related to an anti-sperm auto-monoclonal antibody epitope. J.Reprod.Immunol. 90:202-213, 2011.
  36. Araki Y*, Nonaka D, Tajima A, Maruyama M, Nitto T, Ishikawa H, Yoshitake H, Yoshida E, Kuronaka N, Asada K, Yanagida M, Nojima M, Yoshida K, Takamori K, Hashiguchi T, Maruyama I, Lee L-J, Tanaka K. Quantitative peptidomic analysis by a newly developed one-step direct transfer technology without depletion of major blood proteins: Its potential utility for monitoring of pathophysiological status in pregnancy-induced hypertension. Proteomics 11:2727-2737, 2011.
  37. Honda M*, Asai T, Umemoto T, Araki Y, Oku N, Tanaka M. Supressioion of choroidal neovascularization by single intravitreal injection of APRPG-modified liposomes encapsulating SU5416. Arch Ophthalmol 129: 317-321, 2011.
  38. Lei Z*, Lin J, Li X, Li S, Zhou H, Araki Y, Lan Z-J. Postnatal male germ cell expression of the Cre recombinase in Tex101-iCre transgenic mice. Genesis 48: 717-722, 2010.
  39. Fujiwara H, Ideta A, Araki Y, Takao Y, Sato Y, Horie A, Tsunoda N, Aoyagi Y, Konishi I. Possible contribution of circulating blood cells to embryo implantation. Indian J.Physiol.Pharmacol. 54, Suppl 1:51-60, 2010.
  40. Maruyama M, Yoshitake H, Tsukamoto H, Takamori K, Araki Y*. Molecular expression of Ly6k, a glycosylphosphatidyl-inositol anchored membrane protein on the mouse testicular germ cells. Biochem.Biophys.Res.Commun. 402:75-81, 2010.
  41. Wakabayashi I*, Araki Y. Influences of gender and age on relationships between alcohol drinking and atherosclerotic risk factors. Alcohol.Clin.Exp.Res. 34:S54-60, 2010.
  42. Yamatoya K, Yoshida K, Ito C, Maekawa M, Yanagida M, Takamori K, Ogawa H, Araki Y, Miyado K, Toyama Y, Toshimori K*. Equatorin: identification and characterization of the epitope of the MN9 antibody in the mouse. Biol.Reprod. 81:889-897, 2009.
  43. Fujiwara H, Araki Y, Toshimori K. Is the zona pellucida an intrinsic source of signals activating maternal recognition of the developing mammalian embryo? J.Reprod.Immunol. 81:1-8, 2009.
  44. Shirai Y, Yoshitake H, Maruyama M, Takamori K, Ogawa H, Hasagawa A, Araki Y*. Distribution of molecular epitope for Ts4, an anti-sperm auto-monoclonal antibody in the fertilization process. J.Reprod.Dev. 55:240-246, 2009.
  45. Fujiwara H*, Ideta A, Araki Y, Takao Y, Sato Y, Tsunoda N, Aoyagi Y, Konishi I. Immune system cooperatively supports endocrine system-primed embryo implantation. J.Mammal.Ova.Res. 26:122-128, 2009.
  46. Wakabayashi I*, Araki Y. Associations of alcohol drinking with blood pressure and serum lipids in female smokers and nonsmokers. Gender Med. 6:290-299, 2009.
  47. Yoshitake H, Tsukamoto H, Maruyama-Fukushima M, Takamori K, Ogawa H, Araki Y*. TEX101, a germ cell marker glycoprotein is associated with lymphocyte antigen 6 complex locus k within the mouse testis. Biochem.Biophys.Res.Commun. 372:277-282, 2008.
  48. Yoshitake H, Shirai Y, Mochizuki Y, Iwanari H, Tsubamoto H, Koyama K, Takamori K, Ogawa H, Hasegawa A, Kodama T, Hamakubo T, Araki Y*. Molecular diversity of TEX101, a marker glycoprotein for germ cells monitored with monoclonal antibodies: Variety of the molecular characteristics according to its subcellular localization within the mouse testis. J.Reprod.Immunol. 79:1-11, 2008.
  49. Yoshitake H, Takahashi M, Ishikawa H, Nojima M, Iwanari H, Watanabe A, Aburatani H, Yoshida K, Ishi K, Takamori K, Ogawa H, Hamakubo T, Kodama T, Araki Y*. Aldo-keto reductase family 1, member B10 in uterine carcinomas: a potential risk factor of recurrence after surgical therapy in cervical cancer. Int.J.Gynecol.Cancer 17: 1300-1306, 2007.
  50. Nitto T, Takeda Y, Yoshitake H, Sendo F, Araki Y*. Structural divergence of GPI-80 in activated neutrophils. Biochem.Biophys.Res.Commun. 359:227-233, 2007.
  51. Tsukamoto H, Takizawa T, Takamori K, Ogawa H, Araki Y*. Genomic organization and structure of the 5'-flanking region of the TEX101 gene: Alternative promoter usage and splicing generate transcript variants with distinct 5'-untranslated region. Mol.Reprod.Dev. 74:154-162, 2007.
  52. Suzuki K, Yu X, Chaurand P, Araki Y, Lareyre JJ, Caprioli RM, Orgebin-Crist MC, Matusik RJ. Epididymis-specific lipocalin promoters. Asian J.Androl. 9:515-521, 2007.
  53. Jin H, Yoshitake H, Tsukamoto H, Takahashi M, Mori M, Takizawa T, Takamori K, Ogawa H, Kinoshita K, Araki Y. Molecular characterization of a germ cell-specific antigen, TEX101, from mouse testis. Zygote 14:201-208, 2006.
  54. Tsukamoto H, Yoshitake H, Mori M, Yanagida M, Takamori K, Ogawa H, Takizawa T, Araki Y*. Testicular proteins associated with the germ cell-specific protein, TEX101: Involvement of cellubrevin in TEX101-trafficking to the germ cell surface during spermatogenesis. Biochem.Biophys.Res.Commun. 345:229-238, 2006.
  55. Suzuki K, Yu X, Chaurand P, Araki Y, Lareyre JJ, Caprioli RM, Matusik RJ, Orgebin-Crist MC. Epididymis-specific promoter-driven gene targeting: A transcription factor which regulates epididymis-specific gene expression. Mol.Cell.Endocrinol. 250:184-189, 2006.
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