First Author | Herrera E | Year | 1999 |
Journal | EMBO J | Volume | 18 |
Issue | 11 | Pages | 2950-60 |
PubMed ID | 10357808 | Mgi Jnum | J:55545 |
Mgi Id | MGI:1338633 | Doi | 10.1093/emboj/18.11.2950 |
Citation | Herrera E, et al. (1999) Disease states associated with telomerase deficiency appear earlier in mice with short telomeres. EMBO J 18(11):2950-60 |
abstractText | 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. |