Telomeres, or the ends of linear chromosomes, consist of a short sequence (TTAGGG in humans and mice) repeated thousands of times and are complexed with shelterin proteins that protect chromosome ends and are thus critical for maintaining genomic integrity. The Mus Musculus C57BL/6 mouse has telomeres about 5 times longer than those of humans. Interestingly, the Mus Spretus mouse has 5-fold shorter telomeres than Mus Musculus, similar to the telomere length in humans. The Kaestner lab has recently generated an engineered C57BL/6 “telomouse” with human-length telomeres by introducing into Mus Musculus a single amino acid variation in the helicase ‘Regulator of telomere elongation 1’ (RTEL1) identified in Mus Spretus. These RTEL1 mice are fertile and overtly healthy.

The mammalian liver can regenerate following multiple forms of injury. Strikingly, following partial hepatectomy (PHx), where two-thirds of the liver is surgically resected, the remaining lobes of the mouse liver grow to compensate for the excised liver sections within one-week post-surgery. However, the extremely long telomeres of Mus Musculus do not become critically short following only a couple cell divisions. Here, we asked the question whether the shortened telomeres of Rtel1 mice limit cell proliferation during short-term liver regeneration.