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 language | English |
|---|---|
| Pages (from-to) | 2950-2960 |
| Number of pages | 11 |
| Journal | EMBO Journal |
| Volume | 18 |
| Issue number | 11 |
| DOIs | |
| Publication status | Published - 1999 Jun 1 |
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All Science Journal Classification (ASJC) codes
- Neuroscience(all)
- Molecular Biology
- Biochemistry, Genetics and Molecular Biology(all)
- Immunology and Microbiology(all)
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Disease states associated with telomerase deficiency appear earlier in mice with short telomeres. / Herrera, Eloísa; Samper, Enrique; Martín-Caballero, Juan; Flores, Juana M.; Lee, Han Woong; Blasco, María A.
In: EMBO Journal, Vol. 18, No. 11, 01.06.1999, p. 2950-2960.Research output: Contribution to journal › Article
TY - JOUR
T1 - Disease states associated with telomerase deficiency appear earlier in mice with short telomeres
AU - Herrera, Eloísa
AU - Samper, Enrique
AU - Martín-Caballero, Juan
AU - Flores, Juana M.
AU - Lee, Han Woong
AU - Blasco, María A.
PY - 1999/6/1
Y1 - 1999/6/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=0033153424&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0033153424&partnerID=8YFLogxK
U2 - 10.1093/emboj/18.11.2950
DO - 10.1093/emboj/18.11.2950
M3 - Article
C2 - 10357808
AN - SCOPUS:0033153424
VL - 18
SP - 2950
EP - 2960
JO - EMBO Journal
JF - EMBO Journal
SN - 0261-4189
IS - 11
ER -