Studies on the Control of Telomere Length and the Effects of Shorter Telomeres on Gene Expression in the Mouse

Abstract

Telomeres are structures located at the ends of our chromosomes that protect against DNA damage and chromosome end-to-end fusions. The length of a telomere is important, as telomeres that are too short can elicit a DNA damage response that can lead to replicative cell senescence. Many studies have been carried out looking at the factors that affect telomere length. Two examples of such factors include ageing and epigenetic state. Telomere shortening has been observed with ageing in human and mouse tissue. However, studies in the human population have been confounded by extensive genetic variation. In inbred mice, whether telomere length changes in somatic and germline tissue with age remains unclear. In this thesis, an ageing study was performed on inbred C57BL/6J mice and telomere length was measured using terminal restriction fragment analysis. Surprisingly, little change in telomere length was found in somatic and germline tissue from these mice. The pattern of telomere lengths in one individual is complex and differs among inbred mice. However, a similar pattern was observed in somatic and germline tissue from the same mouse, confirming previous reports that telomere length is already set early in development and is either occurring in the gametes of the parents or early in the zygote.