PUBLICATION

Telomere length is an epigenetic trait - Implications for the use of telomerase-deficient organisms to model human disease

Authors
Henriques, C.M., Ferreira, M.G.
ID
ZDB-PUB-240306-2
Date
2024
Source
Disease models & mechanisms   17(3): (Journal)
Registered Authors
Ferreira, Miguel Godinho
Keywords
Ageing, Epigenetic inheritance, Telomerase, Telomere length, Zebrafish
MeSH Terms
  • Animals
  • Epigenesis, Genetic
  • Humans
  • Phenotype
  • Telomerase*/genetics
  • Telomere/genetics
  • Zebrafish/genetics
PubMed
38441152 Full text @ Dis. Model. Mech.
Abstract
Telomere length, unlike most genetic traits, is epigenetic, in the sense that it is not fully coded by the genome. Telomeres vary in length and randomly assort to the progeny leaving some individuals with longer and others with shorter telomeres. Telomerase activity counteracts this by extending telomeres in the germline and during embryogenesis but sizeable variances remain in telomere length. This effect is exacerbated by the absence of fully active telomerase. Telomerase heterozygous animals (tert+/-) have reduced telomerase activity and their telomeres fail to be elongated to wild-type average length, meaning that - with every generation - they decrease. After a given number of successive generations of telomerase-insufficient crosses, telomeres become critically short and cause organismal defects that, in humans, are known as telomere biology disorders. Importantly, these defects also occur in wild-type (tert+/+) animals derived from such tert+/- incrosses. Despite these tert+/+ animals being proficient for telomerase, they have shorter than average telomere length and, although milder, develop phenotypes that are similar to those of telomerase mutants. Here, we discuss the impact of this phenomenon on human pathologies associated with telomere length, provide a brief overview of telomere biology across species and propose specific measures for working with telomerase-deficient zebrafish.
Genes / Markers
Figures
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Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping