Vav-iCre-Mediated Deletion of TFAM Is Not Recoverable and Is Consistent with Embryonic Lethality

Mar 28, 2026Genes

Deleting TFAM in blood cell precursors causes embryo death that cannot be reversed

AI simplified

Longevity & Aging on OpenScience ↗PubMed ↗DOI ↗OA ↗

Abstract

Loss of the TFAM protein in immune cells may lead to embryonic lethality, as no mutant pups were born.

DNA damage is linked to aging, cancer, and other diseases.
Mitochondrial dysfunction and cellular senescence are associated with DNA damage.
Both nuclear and mitochondrial genome instability contribute to aging in the hematopoietic system.
Loss of TFAM in T cells results in premature immune aging.
Mice lacking SIRT6 in all immune cells were viable and born at expected rates.

AI simplified

Genome stability is the cornerstone of cellular health, and imbalances can cause a number of outcomes, including aging, cancer, and other pathologies. DNA damage is a strong driver of both cellular senescence and mitochondrial dysfunction, two other key hallmarks of aging. Both nuclear and mitochondrial genome instability have been shown to drive aging in the hematopoietic system, which then propagates to non-lymphoid tissues, enhancing morbidity and mortality. The loss of TFAM, a key regulator of mitochondrial DNA replication and nucleoid stability, in T cells has been shown to cause mitochondrial dysfunction, leading to premature immune aging and eventual systemic aging. We sought to investigate whether the loss of TFAM in all immune cells would have a comparable or stronger effect on both the immune system and parenchyma. To address this, we attempted to generate;mice, which are deficient in TFAM in all immune cells. However, this genotype was unrecoverable as no mutant pups were born, suggesting embryonic lethality. Conversely, we generated mice lacking SIRT6, a nuclear DNA repair enzyme that also regulates mitochondrial homeostasis, in all immune cells and found them to be viable and born at expected Mendelian frequencies. Our findings demonstrate the necessity of mitochondrial genome maintenance and homeostasis repair in immunity. Vav-iCre +/-Tfam fl/fl

Full Text

Full text is available at the source.

View full text ↗

Vav-iCre-Mediated Deletion of TFAM Is Not Recoverable and Is Consistent with Embryonic Lethality

Abstract

Full Text

You found one interesting study. We’ll send the next 7.

what lands in your inbox each week:

Recent issues from the longevity & aging brief

Abstract

Full Text

Related papers

You found one interesting study. We’ll send the next 7.

what lands in your inbox each week:

Recent issues from the longevity & aging brief