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2003 | 50 | 2 |

Tytuł artykułu

Expression of a constitutively active mutant of heat shock factor 1 under the control of testis-specific hst70 gene promoter in transgenic mice induces degeneration of seminiferous epithelium

Warianty tytułu

Języki publikacji

EN

Abstrakty

EN
Heat shock activates in somatic cells a set of genes encoding heat shock proteins which function as molecular chaperones. The basic mechanism by which these genes are activated is the interaction of the specific transcription factor HSF1 with a regula­tory DNA sequence called heat shock element (HSE). In higher eukaryotes HSF1 is present in unstressed cells as inactive monomers which, in response to cellular stress, aggregate into transcriptionally competent homotrimers. In the present paper we showed that the expression of a transgene encoding mutated constitutively active HSF1 placed under the control of a spermatocyte-specific promoter derived from the hst70 gene severely affects spermatogenesis. We found the testes of transgenic mice to be significantly smaller than those of wild-type males and histological analysis showed massive degeneration of the seminiferous epithelium. The lumen of tubules was devoid of spermatids and spermatozoa and using the TUNEL method we demonstrated a high rate of spermatocyte apoptosis. The molecular mechanism by which constitutively active HSF1 arrests spermatogenesis is not known so far. One can assume that HSF1 can either induce or repress so far unknown target genes involved in germ cell apoptosis.

Wydawca

-

Rocznik

Tom

50

Numer

2

Opis fizyczny

p.535-541,fig.

Twórcy

autor
  • Center of Oncology, Maria Sklodowska-Curie Memorial Institute, 44-100 Gliwice, Poland
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autor

Bibliografia

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  • Krawczyk Z, Wisniewski J, Biesiada E. (1987) A hsp70-related gene is constitutively highly expressed in testis of rat and mouse. Mol Biol Rep.; 12: 27-34.
  • Lue YH, Hikim AP, Swerdloff RS, Im P, Taing KS, Bui T, Leung A, Wang C. (1999) Single exposure to heat induces stage-specific germ cell apoptosis in rats: role of intratesticular testosterone on stage specificity. Endocrinology.; 140: 1709-17.
  • Matsui Y. (1998) Regulation of germ cell death in mammalian gonads. APMIS.; 106: 142-8.
  • Matsumoto M, Fujimoto H. (1990) Cloning of a hsp70-related gene expressed in mouse spermatids. Biochem Biophys Res Commun.; 166: 43-9.
  • Nakai A, Suzuki M, Tanabe M. (2000) Arrest of spermatogenesis in mice expressing an active heat shock transcription factor 1. EMBO J.; 19: 1545-54.
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  • Singer-Sam J, Robinson MO, Bellve AR, Simon MI, Riggs AD. (1990) Measurement by quantitative PCR of changes in HPRT, PGK-1, PGK-2, APRT, MTase, and Zfy gene transcripts during mouse spermatogenesis. Nucleic Acids Res.; 18: 1255-9.
  • Scieglinska D, Widlak W, Rusin M, Markkula M, Krawczyk Z. (1997) Expression of the testis-specific HSP70-related gene (hst70 gene) in somatic non-testicular rat tissues revealed by RT-PCR and transgenic mice analysis. Cell Biol Int.; 21: 813-21.
  • Scieglinska D, Widlak W, Konopka W, Poutanen M, Rahman N, Huhtaniemi I, Krawczyk Z. (2001) Structure of the 5' region of the hst70 gene transcription unit: presence of an intron and multiple transcription sites. Biochem J.; 359: 129-37.
  • Walter L, Rauch F, Gunther E. (1994) Comparative analysis of the three major histocompatibility complex-linked heat shock protein 70 (Hsp70) genes of the rat. Immunogenetics.; 40: 325-30.
  • Widlak W, Markkula M, Krawczyk Z, Huhtaniemi I. (1994) Functional analysis of spermatocyte- specific hst70 gene promoter in transgenic mice. Acta Biochim Polon.; 41: 103-5.
  • Widlak W, Markkula M, Krawczyk Z, Kananen K, Huhtaniemi I. (1995) A 252 bp upstream region of the rat spermatocyte- specific hst70 gene is sufficient to promote expression of the hst70-CAT hybrid gene in testis and brain of transgenic mice. Biochim Biophys Acta.; 1264: 191-200.
  • Wisniewski J, Kordula T, Krawczyk Z. (1990). Isolation and nucleotide sequence analysis of rat testis-specific major heat shock (hsp70)-related gene. Biochim Biophys Acta.; 1048: 93-9.
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Bibliografia

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