Disease states associated with telomerase deficiency appear earlier in mice with short telomeres

Eloísa Herrera, Enrique Samper, Juan Martín-Caballero, Juana M. Flores, Han Woong Lee, María A. Blasco

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Abstract

Mice deficient for the mouse telomerase RNA (mTR(-/-)) and lacking telomerase activity can only be bred for approximately six generations due to decreased male and female fertility and to an increased embryonic lethality associated with a neural tube closure defect. Although late generation mTR(-/-) mice show defects in the hematopoietic system, they are viable to adulthood, only showing a decrease in viability in old age. To assess the contribution of genetic background to the effect of telomerase deficiency on viability, we generated mTR(-/-) mutants on a C57BL6 background, which showed shorter telomeres than the original mixed genetic background C57BL6/129Sv. Interestingly, these mice could be bred for only four generations and the survival of late generation mTR(-/-) mice decreased dramatically with age as compared with their wild-type counterparts. Fifty percent of the generation 4 mice die at only 5 months of age. This decreased viability with age in the late generation mice is coincident with telomere shortening, sterility, splenic atrophy, reduced proliferative capacity of B and T cells, abnormal hematology and atrophy of the small intestine. These results indicate that telomere shortening in mTR(-/-) mice leads to progressive loss of organismal viability.

Original languageEnglish
Pages (from-to)2950-2960
Number of pages11
JournalEMBO Journal
Volume18
Issue number11
DOIs
Publication statusPublished - 1999 Jun 1

All Science Journal Classification (ASJC) codes

  • Neuroscience(all)
  • Molecular Biology
  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)

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    Herrera, E., Samper, E., Martín-Caballero, J., Flores, J. M., Lee, H. W., & Blasco, M. A. (1999). Disease states associated with telomerase deficiency appear earlier in mice with short telomeres. EMBO Journal, 18(11), 2950-2960. https://doi.org/10.1093/emboj/18.11.2950