Effectors of mammalian telomere dysfunction: A comparative transcriptome analysis using mouse models

Sonia Franco, Andrés Canela, Peter Klatt, María A. Blasco

Research output: Contribution to journalArticle

Abstract

Critical telomere shortening in the absence of telomerase in late generation Terc-/- mice (G3 Terc-/-) or loss of telomere capping due to abrogation of the DNA repair/telomere binding protein Ku86 (Ku86-/- mice) results in telomere dysfunction and organismal premature aging. Here, we report on genome-wide transcription in mouse G3 Terc-/-, Ku86-/- and G3 Terc-/-/Ku86-/- germ cells using high-density oligonucleotide microarrays. Although a few transcripts are modulated specifically in Ku86- or Terc-deficient cells, the observed transcriptional response is mainly inductive and qualitatively similar for all three genotypes, with highest transcriptional induction observed in double mutant G3 Terc-/-/Ku86-/- cells compared with either single mutant. Analysis of 92 known genes induced in G3 Terc-/-/Ku86-/- germ cells compared with wild-type cells shows predominance of genes involved in cell adhesion, cell-to-cell and cell-to-matrix communication, as well as increased metabolic turnover and augmented antioxidant responses. In addition, the data presented in this study support the view that telomere dysfunction induces a robust compensatory response to rescue impaired germ cell function through the induction of survival signals related to the PI3-kinase pathway, as well as by the coordinated upregulation of transcripts that are essential for mammalian spermatogenesis.

Original languageEnglish (US)
Pages (from-to)1613-1626
Number of pages14
JournalCarcinogenesis
Volume26
Issue number9
DOIs
StatePublished - Sep 2005
Externally publishedYes

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Telomere
Gene Expression Profiling
Germ Cells
Telomere-Binding Proteins
Premature Aging
Telomere Shortening
Telomerase
Spermatogenesis
Oligonucleotide Array Sequence Analysis
Phosphatidylinositol 3-Kinases
Cell Adhesion
DNA Repair
Genes
Up-Regulation
Antioxidants
Communication
Genotype
Genome

ASJC Scopus subject areas

  • Cancer Research

Cite this

Effectors of mammalian telomere dysfunction : A comparative transcriptome analysis using mouse models. / Franco, Sonia; Canela, Andrés; Klatt, Peter; Blasco, María A.

In: Carcinogenesis, Vol. 26, No. 9, 09.2005, p. 1613-1626.

Research output: Contribution to journalArticle

Franco, Sonia ; Canela, Andrés ; Klatt, Peter ; Blasco, María A. / Effectors of mammalian telomere dysfunction : A comparative transcriptome analysis using mouse models. In: Carcinogenesis. 2005 ; Vol. 26, No. 9. pp. 1613-1626.
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