TY - JOUR
T1 - Inhibition of experimental liver cirrhosis in mice by telomerase gene delivery
AU - Rudolph, Karl Lenhard
AU - Chang, Sandy
AU - Millard, Melissa
AU - Schreiber-Agus, Nicole
AU - DePinho, Ronald A.
PY - 2000/2/18
Y1 - 2000/2/18
N2 - Accelerated telomere loss has been proposed to be a factor leading to end-stage organ failure in chronic diseases of high cellular turnover such as liver cirrhosis. To test this hypothesis directly, telomerase-deficient mice, null for the essential telomerase RNA (mTR) gene, were subjected to genetic, surgical, and chemical ablation of the liver. Telomere dysfunction was associated with defects in liver regeneration and accelerated the development of liver cirrhosis in response to chronic liver injury. Adenoviral delivery of mTR into the livers of mTR(-/-) mice with short dysfunctional telomeres restored telomerase activity and telomere function, alleviated cirrhotic pathology, and improved liver function. These studies indicate that telomere dysfunction contributes to chronic diseases of continual cellular loss- replacement and encourage the evaluation of 'telomerase therapy' for such diseases.
AB - Accelerated telomere loss has been proposed to be a factor leading to end-stage organ failure in chronic diseases of high cellular turnover such as liver cirrhosis. To test this hypothesis directly, telomerase-deficient mice, null for the essential telomerase RNA (mTR) gene, were subjected to genetic, surgical, and chemical ablation of the liver. Telomere dysfunction was associated with defects in liver regeneration and accelerated the development of liver cirrhosis in response to chronic liver injury. Adenoviral delivery of mTR into the livers of mTR(-/-) mice with short dysfunctional telomeres restored telomerase activity and telomere function, alleviated cirrhotic pathology, and improved liver function. These studies indicate that telomere dysfunction contributes to chronic diseases of continual cellular loss- replacement and encourage the evaluation of 'telomerase therapy' for such diseases.
UR - http://www.scopus.com/inward/record.url?scp=0034681457&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0034681457&partnerID=8YFLogxK
U2 - 10.1126/science.287.5456.1253
DO - 10.1126/science.287.5456.1253
M3 - Article
C2 - 10678830
AN - SCOPUS:0034681457
SN - 0036-8075
VL - 287
SP - 1253
EP - 1258
JO - Science
JF - Science
IS - 5456
ER -