Essential role of mouse telomerase in highly proliferative organs.
We have investigated the role of the enzyme telomerase in highly proliferative organs in successive generations of mice lacking telomerase RNA. Late-generation animals exhibited defective spermatogenesis, with increased programmed cell death (apoptosis) and decreased proliferation in the testis. The proliferative capacity of haematopoietic cells in the bone marrow and spleen was also compromised. These progressively adverse effects coincided with substantial erosion of telomeres (the termini of eukaryotic chromosomes) and fusion and loss of chromosomes. These findings indicate an essential role for telomerase, and hence telomeres, in the maintenance of genomic integrity and in the long-term viability of high-renewal organ systems.
Lee
H W
HW
Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, New York 10461, USA.
Blasco
M A
MA
Gottlieb
G J
GJ
Horner
J W
JW
Greider
C W
CW
DePinho
R A
RA
D000818:Animals; D017209:Apoptosis; D002455:Cell Division / Q000502:physiology*; D002871:Chromosome Banding; D005314:Embryonic and Fetal Development / Q000502:physiology; D005260:Female; D006410:Hematopoiesis / Q000502:physiology; D006412:Hematopoietic Stem Cells / Q000502:physiology; D008214:Lymphocytes / Q000502:physiology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D010053:Ovary / Q000166:cytology / Q000502:physiology; D019098:Telomerase / Q000172:deficiency / Q000502:physiology*; D016615:Telomere; D013737:Testis / Q000166:cytology / Q000502:physiology
D019098:Telomerase