Disease states associated with telomerase deficiency appear earlier in mice with short telomeres - PubMed (original) (raw)

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

E Herrera et al. EMBO J. 1999.

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.

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References

    1. Proc Natl Acad Sci U S A. 1994 Sep 13;91(19):8861-5 - PubMed
    1. J Cell Biol. 1999 Feb 22;144(4):589-601 - PubMed
    1. Cell. 1995 Jun 2;81(5):677-86 - PubMed
    1. Nature. 1995 Aug 3;376(6539):403-9 - PubMed
    1. Science. 1995 Sep 1;269(5228):1236-41 - PubMed

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