Influences of inbreeding and genetics on telomere length in mice

Abstract

We measured telomere lengths of blood leukocytes in several inbred and outbred mammalian species, using a telomere-specific fluorescent probe and flow cytometry. Humans, non-human primates, and three outbred populations of Peromyscus mice ( Peromyscus leucopus, Peromyscus maniculatus, and Peromyscus polionotus) have short telomeres. Two common strains of laboratory mice, C57BL/6J and DBA/2J, have telomeres several times longer than most other mammals surveyed. Moreover, the two inbred laboratory mouse strains display significantly different telomere lengths, suggesting the existence of strain-specific genetic determinants. To further examine the effects of inbreeding, we studied three Peromyscus leucopus inbred lines (GS109, GS16A1, and GS16B), all derived from the outbred P. leucopus stock. Telomeres of all three inbred lines are significantly lengthened relative to outbred P. leucopus, and the three lines display strain-specific significantly different telomere lengths, much like the C57BL/6J and DBA/2J strains of M. musculus. To further characterize the genetic inheritance of telomere length, we carried out several crosses to obtain hybrid F(1) mice between parental strains displaying the phenotype of long and short telomeres. In all F(1) mice assayed, peripheral blood leukocyte telomere length was intermediate to that of the parents. Additionally, we generated F(2) mice from a cross of the ( P. leucopus outbred x GS16B)F(1). Based on the distribution of telomere length in the F(2) population, we determined that more than five loci contribute to telomere length regulation in Peromyscus. We concluded that inbreeding, through unknown mechanisms, results in the elongation of telomeres, and that telomere length for a given species and/or sub-strain is genetically determined by multiple segregating loci.

Mother–offspring and nest-mate resemblance but no heritability in early-life telomere length in white-throated dippers

“…This positive relationship is surprising, as longer telomeres have been associated with increased survival rate and lifespan [4,5], whereas survival and lifespan are typically lower in inbred individuals (for review, see [62]). Interestingly, however, it is in line with findings in laboratory mouse strains [63] and domesticated chicken lines [64]. Furthermore, knowledge about the relationship between telomere length and fitnessrelated traits such as fecundity is still limited (but see [9]), and the longer telomeres of inbred nestlings may be a by-product of inbreeding effects on factors associated with telomere elongation.…”

Is telomere erosion a mechanism of species extinction?

“…Hemann and Greider suggested that telomere elongation in established strains of lab mice might have resulted from extensive breeding of an isolated colony. In a more recent paper, Manning and colleagues go even further by claiming that inbreeding, through unknown mechanisms, results in the elongation of telomeres (Manning et al, 2002). This would be in agreement with the current view of how new species emerge.…”

Pancreatic beta cell senescence contributes to the pathogenesis of type 2 diabetes in high-fat diet-induced diabetic mice

“…Senescence of human primary pancreatic beta cells is caused by a telomere-independent pathway because senescence is not prevented by the expression of telomerase, which extends telomere length [34]. Additionally, telomere length in mice is much longer than in humans, suggesting that telomeres are not related to cellular senescence in mice [35,36]. Many studies demonstrate that cellular senescence is caused by ROS and is mediated Fig.…”