Disease states associated with telomerase deficiency appear earlier in mice with short telomeres.
EMBO J
; 18(11): 2950-60, 1999 Jun 01.
Article
en En
| MEDLINE
| ID: mdl-10357808
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.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Telómero
/
Telomerasa
/
Infertilidad
/
Longevidad
Tipo de estudio:
Risk_factors_studies
Límite:
Animals
Idioma:
En
Revista:
EMBO J
Año:
1999
Tipo del documento:
Article
País de afiliación:
España
Pais de publicación:
Reino Unido