Regulation of murine telomere length by Rtel: An essential gene encoding a helicase-like protein

Hao Ding, Mike Schertzer, Xiaoli Wu, Marina Gertsenstein, Sara Selig, Makoto Kammori, Reza Pourvali, Steven Poon, Irma Vulto, Elizabeth Chavez, Patrick P.L. Tam, Andras Nagy, Peter M. Lansdorp

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Abstract

Little is known about the genes that regulate telomere length diversity between mammalian species. A candidate gene locus was previously mapped to a region on distal mouse Chr 2q. Within this region, we identified a gene similar to the dog-1 DNA helicase-like gene in C. elegans. We cloned this Regulator of telomere length (Rtel) gene and inactivated its expression in mice. Rtel -/- mice died between days 10 and 11.5 of gestation with defects in the nervous system, heart, vasculature, and extraembryonic tissues. Rtel -/- embryonic stem cells showed telomere loss and displayed many chromosome breaks and fusions upon differentiation in vitro. Crosses of Rtel+/- mice with Mus spretus showed that Rtel from the Mus musculus parent is required for telomere elongation of M. spretus chromosomes in F1 cells. We conclude that Rtel is an essential gene that regulates telomere length and prevents genetic instability.

Original languageEnglish
Pages (from-to)873-886
Number of pages14
JournalCell
Volume117
Issue number7
DOIs
Publication statusPublished - 25 Jun 2004
Externally publishedYes

Cite this

Ding, H., Schertzer, M., Wu, X., Gertsenstein, M., Selig, S., Kammori, M., Pourvali, R., Poon, S., Vulto, I., Chavez, E., Tam, P. P. L., Nagy, A., & Lansdorp, P. M. (2004). Regulation of murine telomere length by Rtel: An essential gene encoding a helicase-like protein. Cell, 117(7), 873-886. https://doi.org/10.1016/j.cell.2004.05.026