Molecular Biology Reports

, Volume 40, Issue 2, pp 1905–1910

Overexpression of human SPATA17 protein induces germ cell apoptosis in transgenic male mice



SPATA17 is a new testis-specific-expressed gene that is involved in Spermatogenesis process. Previous studies show that SPATA17 was involved in acceleration of cell apoptosis in GC-1 cell lines. To further investigate specific roles of SPATA17 in Spermatogenesis in vivo, we generated transgenic mice in which the human SPATA17 gene was expressed specifically in spermatocytes using the human phosphoglycerate kinase 2 (PGK2) promoter. The SPATA17 transgenic mice did not show any significant defect in gross testicular anatomy as well as in fertility. However, a significant increase was observed in defective spermatogenic cells, such as apoptotic cells in the SPATA17 transgenic mice. These results revealed that elevated production of the SPATA17 protein disturbed the normal development of male germ cells.


Cell apoptosis SPATA17 Spermatogenesis Transgenic Mouse 


  1. 1.
    Matsui Y (1998) Regulation of germ cell death in mammalian gonads. APMIS 106:142–147PubMedCrossRefGoogle Scholar
  2. 2.
    Print CG, Loveland KL (2000) Germ cell suicide: new insights into apoptosis during spermatogenesis. Bioessays 22:423–430PubMedCrossRefGoogle Scholar
  3. 3.
    Hiroshi O, Shinichi A, Yoshitake N (2003) Functional analysis of the p53 gene in apoptosis induced by heat stress or loss of stem cell factor signaling in mouse male germ cells. Biol Reprod 68:2249–2254Google Scholar
  4. 4.
    Shukla KK, Mahdi AA, Rajender S (2012) Apoptosis, spermatogenesis and male infertility. Front Biosci 1(4):746–754Google Scholar
  5. 5.
    Beumer TL, Roepers HL, Gademan LS, Rutgers DH, deRooij DG (1997) P21(Cip1/WAF1) expression in the mouse testis before and after X irradiation. Mol Reprod Dev 47:240–247PubMedCrossRefGoogle Scholar
  6. 6.
    Richburg JH (2000) The relevance of spontaneous- and chemically-induced alterations in testicular germ cell apoptosis to toxicology. Toxicol Lett 112–113:79–86PubMedCrossRefGoogle Scholar
  7. 7.
    Sinha Hikim AP, Swerdloff RS (1999) Hormonal and genetic control of germ cell apoptosis in the testis. Rev Reprod 4:38–47PubMedCrossRefGoogle Scholar
  8. 8.
    Packer AI, Besmer P, Bachvarova RF (1995) Kit ligand mediates survival of type A spermatogonia and dividing spermatocytes in postnatal mouse testes. Mol Reprod Dev 42:303–310PubMedCrossRefGoogle Scholar
  9. 9.
    Yan W, Suominen J, Toppari J (2000) Stem cell factor protects germ cells from apoptosis in vitro. J Cell Sci 113:161–168PubMedGoogle Scholar
  10. 10.
    Deng Y, Nie DS, Wang J, Tan XJ, Nie ZY, Yang HM, Hu LS, Lu GX (2005) Molecular cloning of MSRG-11 gene related to apoptosis of mouse spermatogenic cells. Acta Biochim Biophys Sin (Shanghai) 37(3):159–166Google Scholar
  11. 11.
    Deng Y, Hu LS, Lu GX (2006) Expression and identification of a novel apoptosis gene SPATA17 (MSRG-11) in mouse spermatogenic cells. Acta Biochim Biophys Sin (Shanghai) 39(1):37–45CrossRefGoogle Scholar
  12. 12.
    Tascou S, Nayernia K, Meinhardt A, Schweyer S, Engel W, Trappe R, Burfeind P (2001) Targeted expression of SV40 large tumour antigen (TAg) induces a transient enhancement of spermatocyte proliferation and apoptosis. Mol Hum Reprod 7:1123–1131PubMedCrossRefGoogle Scholar
  13. 13.
    Kaczmarek K, Studencka M, Meinhardt A, Wieczerzak K, Thoms S, Engel W, Grzmil P (2011) Cell Overexpression of peroxisomal testis-specific 1 protein induces germ cell apoptosis and leads to infertility in male mice. Mol Biol Cell 22(10):1766–1779PubMedCrossRefGoogle Scholar
  14. 14.
    Burnicka-Turek O, Shirneshan K, Paprotta I, Grzmil P, Meinhardt A, Engel W, Adham IM (2009) Inactivation of insulin-like factor 6 disrupts the progression of spermatogenesis at late meiotic prophase. Endocrinology 150(9):4348–4357PubMedCrossRefGoogle Scholar
  15. 15.
    Robinson M, McCarrey J, Simon M (1989) Transcriptional regulatory regions of testis-specific PGK2 defined in transgenic mice. Proc Natl Acad Sci USA 86:8437–8441PubMedCrossRefGoogle Scholar
  16. 16.
    Toshinobu M, Akira T, Yasushi M, Eitetsu K, Naoko S, Hiroe M, Hisashi S, Mikio N, Akihiko O, Kazuo S (2009) A single nucleotide polymorphism in SPATA17 may be a genetic risk factor for Japanese patients with meiotic arrest. Asian J Androl 11:623–628CrossRefGoogle Scholar
  17. 17.
    Yin Y, Dewolf WC, Morgentaler A (1998) Experimental cryptorchidism induces testicular germ cell apoptosis by p53-dependent and -independent pathways in mice. Biol Reprod 58(2):492–496PubMedCrossRefGoogle Scholar
  18. 18.
    Codelia VA, Cisterna M, Alvarez AR, Moreno RD (2010) p73 participates in male germ cells apoptosis induced by etoposide. Mol Hum Reprod 16(10):734–742PubMedCrossRefGoogle Scholar
  19. 19.
    Lee J, Richburg JH, Younkin SC, Boekelheide K (1997) The Fas system is a key regulator of germ cell apoptosis in the testis. Endocrinology 138(5):2081–2088PubMedCrossRefGoogle Scholar
  20. 20.
    Yamamoto CM, Sinha Hikim AP, Huynh PN, Shapiro B, Lue Y, Salameh WA, Wang C (2000) Redistribution of Bax is an early step in an apoptosis pathway leading to germ cell death in rats, triggered by mild testicular hyperthermia. Biol Reprod 63(6):1683–1690PubMedCrossRefGoogle Scholar
  21. 21.
    Rhoads AR, Friedberg F (1997) Sequence motifs for calmodulin recognition. FASEB J 11(5):331–340PubMedGoogle Scholar
  22. 22.
    Wang X, Kleerekoper QK, Xiong LW, Putkey JA (2010) Intrinsically disordered PEP-19 confers unique dynamic properties to apo and calcium calmodulin. Biochemistry 49(48):10287–10297PubMedCrossRefGoogle Scholar
  23. 23.
    Clayton DF, George JM, Mello CV, Siepka SM (2009) Conservation and expression of IQ-domain-containing calpacitin gene products (neuromodulin/GAP-43, neurogranin/RC3) in the adult and developing oscine song control system. Dev Neurobiol 69(2–3):124–140PubMedCrossRefGoogle Scholar
  24. 24.
    Kang CH, Jung WY, Kang YH, Kim JY, Kim DG, Jeong JC (2006) AtBAG6, a novel calmodulin-binding protein, induces programmed cell death in yeast and plants. Cell Death Differ 13:84–95PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media Dordrecht 2012

Authors and Affiliations

  1. 1.Department of Chemistry and Chemical EngineeringHunan Institute of Science and TechnologyYueYangChina
  2. 2.The Second People’s Hospital of YueYangYueYangChina

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