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Male sterility and enhanced radiation sensitivity in TLS(-/-) mice

M Kuroda1, J Sok, L Webb

  • 1Skirball Institute of Biomolecular Medicine, the Departments of Medicine, Cell Biology and the Kaplan Cancer Center, NYU Medical Center, New York, NY 10016, USA.

The EMBO Journal
|February 2, 2000
PubMed

Insights

The study found that the TLS (FUS) protein is crucial for male fertility and DNA repair. Mice lacking TLS show infertility and increased DNA damage sensitivity, suggesting its role in homologous pairing and recombination.

Area of Science:

  • Molecular Biology
  • Genetics
  • Reproductive Biology

Background:

  • The Translocated Promoter Region (TLS) protein, also known as Fused in Sarcoma (FUS), is an RNA-binding protein.
  • TLS is implicated in human liposarcomas and leukemias due to its role in fusion oncoproteins.

Purpose of the Study:

  • To investigate the function of TLS in male fertility and DNA repair mechanisms.
  • To determine the role of TLS in homologous DNA pairing and recombination.

Main Methods:

  • Generation and analysis of TLS-deficient (TLS(-/-)) mice.
  • Microscopic examination of spermatocyte chromosomal axes.
  • In vitro assays using nuclear extracts to assess DNA pairing activity.
  • Ionizing radiation sensitivity tests on TLS(-/-) mice and fibroblasts.

Main Results:

  • Male mice homozygous for a TLS mutation were sterile.
  • TLS(-/-) spermatocytes exhibited increased unpaired and mispaired chromosomal axes.
  • Nuclear extracts from TLS(-/-) testes lacked activity promoting homologous DNA pairing in vitro.
  • TLS(-/-) mice and fibroblasts showed heightened sensitivity to ionizing irradiation.

Conclusions:

  • TLS plays a critical role in male meiosis and fertility.
  • The findings support a function for TLS in homologous DNA pairing and recombination processes.
  • TLS is involved in DNA repair pathways, as evidenced by increased sensitivity to ionizing radiation.

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