Generation and characterization of telomere length maintenance in tankyrase 2-deficient mice.
Telomere length and function are crucial factors that determine the capacity for cell proliferation and survival, mediate cellular senescence, and play a role in malignant transformation in eukaryotic systems. The telomere length of a specific mammalian species is maintained within a given range by the action of telomerase and telomere-associated proteins. TRF1 is a telomere-associated protein that inhibits telomere elongation by its binding to telomere repeats, preventing access to telomerase. Human TRF1 interacts with tankyrase 1 and tankyrase 2 proteins, two related members of the tankyrase family shown to have poly(ADP-ribose) polymerase activity. Human tankyrase 1 is reported to ADP-ribosylate TRF1 and to down-regulate the telomeric repeat binding activity of TRF1, resulting in telomerase-dependent telomere elongation. Human tankyrase 2 is proposed to have activity similar to that of tankyrase 1, although tankyrase 2 function has been less extensively characterized. In the present study, we have assessed the in vivo function of mouse tankyrase 2 by germ line gene inactivation and show that inactivation of tankyrase 2 does not result in detectable alteration in telomere length when monitored through multiple generations of breeding. This finding suggests that either mouse tankyrases 1 and 2 have redundant functions in telomere length maintenance or that mouse tankyrase 2 differs from human tankyrase 2 in its role in telomere length maintenance. Tankyrase 2 deficiency did result in a significant decrease in body weight sustained through at least the first year of life, most marked in male mice, suggesting that tankyrase 2 functions in potentially telomerase-independent pathways to affect overall development and/or metabolism.
Chiang
Y Jeffrey
YJ
Experimental Immunology Branch, National Cancer Institute, National Institutes of Health, Building 10, 4B36, 9000 Rockville Pike, Bethesda, MD 20892, USA. chiangj@mail.nih.gov
Nguyen
My-Linh
ML
Gurunathan
Sujatha
S
Kaminker
Patrick
P
Tessarollo
Lino
L
Campisi
Judith
J
Hodes
Richard J
RJ
D000818:Animals; D001835:Body Weight / Q000235:genetics; D005260:Female; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D012737:Sex Factors; D038501:Tankyrases / Q000235:genetics* / Q000378:metabolism*; D016615:Telomere / Q000502:physiology*
D038501:Tankyrases; C498822:Tnks protein, mouse; C511054:tankyrase-2, mouse