Addendum: Telomouse—a mouse model with human-length telomeres generated by a single amino acid change in RTEL1

In this article, the authors reported an engineered mouse model, termed 'Telomouse', with a missense mutation in Rtel1 (methionine 492 to a lysine; Rtel1 M492K ).The design of the Telomouse strain was based on the genetic association of Rtel1 with telomere length, as identified by crossing Mus spretus with short telomeres to M. musculus with long telomeres 1 , and on the presence of the Rtel1 M492K variation in the M. spretus Rtel1 transcripts sequences available at the time 2 .The authors hypothesized that this variation was responsible for the shorter telomeres of M. spretus, as compared with M. musculus, and predicted that a M. musculus strain harboring this mutation would also shorten its telomeres.While Telomice homozygous for the Rtel1 M492K mutation indeed shortened their telomeres as predicted, the more recently available M. spretus genome 3 revealed no such variation in Rtel1.Furthermore, the authors obtained DNA samples from two available M. spretus strains 4,5 , PCR-sequenced this part of Rtel1, and found that both strains have a methionine at position 492.M. spretus appears highly heterogenous 6 and the authors cannot exclude the possibility that the original strain used for the cDNA sequencing indeed had a lysine at position 492.However, since two currently used M. spretus strains have short telomeres but not the Rtel1 M492K variation, such a variation cannot explain the short telomeres in this species.Importantly, introducing Rtel1 M492K mutation into M. musculus resulted in short, stable, human-length telomeres in an invaluable model for studying the roles of telomeres in cancer and aging.