A novel inducible mtDNA mutator mouse model to study mitochondrial dysfunction with temporal and spatial control DOI

Hannah Tobias-Wallingford,

Sydney Bartman,

Lauren Gaspar

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2025, Volume and Issue: unknown

Published: April 21, 2025

Abstract Mitochondrial dysfunction is a hallmark of aging and numerous age-related diseases. A wealth studies supports the accumulation mitochondrial DNA (mtDNA) mutations as contributing factor to in disease. One best models study relationship between mtDNA mutator mouse, which expresses proofreading-deficient version polymerase-γ (PolgA). Despite its groundbreaking contributions biology research, this model limited by whole-body mutations, prevents investigation tissue-specific differences dysfunction. To overcome limitation, we developed novel inducible knock-in mouse that allows spatial temporal control enabling precise tissue- time-specific manner. Here, report generation validation through induction via Cre recombinase. Our data demonstrate that, upon induction, recapitulates phenotype original manifesting same behavioral biochemical alterations. This work establishes functionality our highlights value powerful tool for studying impact with enhanced specificity control.

Language: Английский

A novel inducible mtDNA mutator mouse model to study mitochondrial dysfunction with temporal and spatial control DOI

Hannah Tobias-Wallingford,

Sydney Bartman,

Lauren Gaspar

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2025, Volume and Issue: unknown

Published: April 21, 2025

Abstract Mitochondrial dysfunction is a hallmark of aging and numerous age-related diseases. A wealth studies supports the accumulation mitochondrial DNA (mtDNA) mutations as contributing factor to in disease. One best models study relationship between mtDNA mutator mouse, which expresses proofreading-deficient version polymerase-γ (PolgA). Despite its groundbreaking contributions biology research, this model limited by whole-body mutations, prevents investigation tissue-specific differences dysfunction. To overcome limitation, we developed novel inducible knock-in mouse that allows spatial temporal control enabling precise tissue- time-specific manner. Here, report generation validation through induction via Cre recombinase. Our data demonstrate that, upon induction, recapitulates phenotype original manifesting same behavioral biochemical alterations. This work establishes functionality our highlights value powerful tool for studying impact with enhanced specificity control.

Language: Английский

Citations

0