PUBLICATION

Zebrafish as a Model System to Study the Physiological Function of Telomeric Protein TPP1

Authors
Xie, Y., Yang, D., He, Q., and Songyang, Z.
ID
ZDB-PUB-110214-36
Date
2011
Source
PLoS One   6(2): e16440 (Journal)
Registered Authors
Keywords
none
MeSH Terms
  • Amino Acid Sequence
  • Animals
  • Animals, Genetically Modified
  • Base Sequence
  • Embryo, Nonmammalian
  • Embryonic Development/genetics
  • Embryonic Development/physiology
  • Gene Knockdown Techniques
  • Humans
  • Models, Animal*
  • Molecular Sequence Data
  • Sequence Homology, Amino Acid
  • Telomere-Binding Proteins/genetics
  • Telomere-Binding Proteins/metabolism
  • Telomere-Binding Proteins/physiology*
  • Zebrafish/embryology
  • Zebrafish/genetics*
  • Zebrafish/physiology
  • Zebrafish Proteins/genetics
  • Zebrafish Proteins/metabolism
  • Zebrafish Proteins/physiology*
PubMed
21311760 Full text @ PLoS One
Abstract
Telomeres are specialized chromatin structures at the end of chromosomes. Telomere dysfunction can lead to chromosomal abnormalities, DNA damage responses, and even cancer. In mammalian cells, a six-protein complex (telosome/shelterin) is assembled on the telomeres through the interactions between various domain structures of the six telomere proteins (POT1, TPP1, TIN2, TRF1, TRF2 and RAP1), and functions in telomere maintenance and protection. Within the telosome, TPP1 interacts directly with POT1 and TIN2 and help to mediate telosome assembly. Mechanisms of telomere regulation have been extensively studied in a variety of model organisms. For example, the physiological roles of telomere-targeted proteins have been assessed in mice through homozygous inactivation. In these cases, early embryonic lethality has prevented further studies of these proteins in embryogenesis and development. As a model system, zebrafish offers unique advantages such as genetic similarities with human, rapid developmental cycles, and ease of manipulation of its embryos. In this report, we detailed the identification of zebrafish homologues of TPP1, POT1, and TIN2, and showed that the domain structures and interactions of these telosome components appeared intact in zebrafish. Importantly, knocking down TPP1 led to multiple abnormalities in zebrafish embryogenesis, including neural death, heart malformation, and caudal defect. And these embryos displayed extensive apoptosis. These results underline the importance of TPP1 in zebrafish embryogenesis, and highlight the feasibility and advantages of investigating the signaling pathways and physiological function of telomere proteins in zebrafish.
Errata / Notes
Erratum in PLoS One. 2011 Feb 17; 6(2).
The 2nd affiliation for the 4th author was not indicated. Zhou Songyang is affiliated with both 1 State Key laboratory for Biocontrol, Sun Yat-Sen University, Guangzhou, People's Republic of China, and 2 Verna and Marrs McLean Department of Biochemistry and Molecular biology, Baylor College of Medicine, Houston, Texas, United States of America.
Genes / Markers
Figures
Show all Figures
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping