Terc Gene Cluster Variants Predict Liver Telomere Length in Mice.

Area of Science:

• Genetics
• Molecular Biology
• Aging Research

Background:

• Human studies link variants in the TERC gene cluster to telomere length.
• The precise mechanism of this association, particularly regarding linkage disequilibrium with TERC, remains unclear.
• Mouse and human TERC gene cluster organization differs significantly, necessitating model system investigation.

Purpose of the Study:

• To investigate genotype-nicotine interactions on absolute liver telomere length (aTL) in mice.
• To identify candidate single nucleotide polymorphisms (SNPs) in the murine TERC gene cluster associated with aTL.
• To validate the association between TERC gene cluster variants and aTL in an independent mouse cohort.

Main Methods:

• Experiment 1: Assessed genotype-nicotine effects on liver aTL across eight inbred mouse strains.
• Identified candidate SNPs in murine TERC cluster genes (Lrrc31, Lrriq4, Mynn) co-varying with aTL.
• Experiment 2: Tested association of candidate TERC gene cluster variants with liver aTL in a second independent mouse panel.

Main Results:

• Nicotine exposure did not significantly impact liver aTL in any mouse strain.
• Identified significant associations between specific TERC gene cluster SNPs and liver aTL in mice.
• Findings in mice align with human population data, suggesting conserved regulatory mechanisms.

Conclusions:

• TERC gene cluster polymorphisms directly influence telomere length in mice.
• Mice serve as a viable model for studying telomere length regulation by TERC cluster variants.
• Mechanisms independent of linkage disequilibrium between the TERC gene and its cluster likely mediate telomere length regulation.