NDLI: Premature aging in telomerase-deficient zebrafish

Content Provider	PubMed Central
Author	Monique, Anchelin Francisca, Alcaraz-pérez Martínez, Carlos M. Manuel, Bernabé-garcía Mulero, Victoriano Cayuela, María L.
Copyright Year	2013
Abstract	The study of telomere biology is crucial to the understanding of aging and cancer. In the pursuit of greater knowledge in the field of human telomere biology, the mouse has been used extensively as a model. However, there are fundamental differences between mouse and human cells. Therefore, additional models are required. In light of this, we have characterized telomerase-deficient zebrafish (Danio rerio) as the second vertebrate model for human telomerase-driven diseases. We found that telomerase-deficient zebrafish show p53-dependent premature aging and reduced lifespan in the first generation, as occurs in humans but not in mice, probably reflecting the similar telomere length in fish and humans. Among these aging symptoms, spinal curvature, liver and retina degeneration, and infertility were the most remarkable. Although the second-generation embryos died in early developmental stages, restoration of telomerase activity rescued telomere length and survival, indicating that telomerase dosage is crucial. Importantly, this model also reproduces the disease anticipation observed in humans with dyskeratosis congenita (DC). Thus, telomerase haploinsufficiency leads to anticipation phenomenon in longevity, which is related to telomere shortening and, specifically, with the proportion of short telomeres. Furthermore, p53 was induced by telomere attrition, leading to growth arrest and apoptosis. Importantly, genetic inhibition of p53 rescued the adverse effects of telomere loss, indicating that the molecular mechanisms induced by telomere shortening are conserved from fish to mammals. The partial rescue of telomere length and longevity by restoration of telomerase activity, together with the feasibility of the zebrafish for high-throughput chemical screening, both point to the usefulness of this model for the discovery of new drugs able to reactivate telomerase in individuals with DC.
Related Links	http://dx.doi.org/10.1242/dmm.011635
Ending Page	1112
Page Count	12
Starting Page	1101
File Format	PDF
ISSN	17548403
e-ISSN	17548411
Journal	Disease Models & Mechanisms
Issue Number	5
Volume Number	6
Language	English
Publisher	The Company of Biologists Limited
Publisher Date	2013-09-01
Access Restriction	Open
Rights Holder	The Company of Biologists Limited
Subject Keyword	Immunology and Microbiology (miscellaneous) Biochemistry, Genetics and Molecular Biology(all) Medicine (miscellaneous) Neuroscience (miscellaneous) Medicine(all) Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Neuroscience Immunology and Microbiology Medicine Biochemistry, Genetics and Molecular Biology

Sl.	Authority	Responsibilities	Communication Details
1	Ministry of Education (GoI), Department of Higher Education	Sanctioning Authority	https://www.education.gov.in/ict-initiatives
2	Indian Institute of Technology Kharagpur	Host Institute of the Project: The host institute of the project is responsible for providing infrastructure support and hosting the project	https://www.iitkgp.ac.in
3	National Digital Library of India Office, Indian Institute of Technology Kharagpur	The administrative and infrastructural headquarters of the project	Dr. B. Sutradhar bsutra@ndl.gov.in
4	Project PI / Joint PI	Principal Investigator and Joint Principal Investigators of the project	Dr. B. Sutradhar bsutra@ndl.gov.in Prof. Saswat Chakrabarti will be added soon
5	Website/Portal (Helpdesk)	Queries regarding NDLI and its services	support@ndl.gov.in
6	Contents and Copyright Issues	Queries related to content curation and copyright issues	content@ndl.gov.in
7	National Digital Library of India Club (NDLI Club)	Queries related to NDLI Club formation, support, user awareness program, seminar/symposium, collaboration, social media, promotion, and outreach	clubsupport@ndl.gov.in
8	Digital Preservation Centre (DPC)	Assistance with digitizing and archiving copyright-free printed books	dpc@ndl.gov.in
9	IDR Setup or Support	Queries related to establishment and support of Institutional Digital Repository (IDR) and IDR workshops	idr@ndl.gov.in

Premature aging in telomerase-deficient zebrafish

Zebrafish deficient for Muscleblind-like 2 exhibit features of myotonic dystrophy

Building bridges with zebrafish: highlights of the ‘Zebrafish Models in Translational Medicine’ meeting

Spotlight on Zebrafish: Translational Impact

Zebrafish myelination: a transparent model for remyelination?

The zebrafish as a model for cancer

Repairing quite swimmingly: advances in regenerative medicine using zebrafish

Genetic modeling of Li-Fraumeni syndrome in zebrafish

Zebrafish as a model for normal and malignant hematopoiesis

Premature aging in telomerase-deficient zebrafish

Similar Documents

Premature aging in telomerase-deficient zebrafish

Zebrafish deficient for Muscleblind-like 2 exhibit features of myotonic dystrophy

Building bridges with zebrafish: highlights of the ‘Zebrafish Models in Translational Medicine’ meeting

Spotlight on Zebrafish: Translational Impact

Zebrafish myelination: a transparent model for remyelination?

The zebrafish as a model for cancer

Repairing quite swimmingly: advances in regenerative medicine using zebrafish

Genetic modeling of Li-Fraumeni syndrome in zebrafish

Zebrafish as a model for normal and malignant hematopoiesis

Premature aging in telomerase-deficient zebrafish