Establishing an in vivo humanised mouse model for telomere related bone marrow failure syndromes.

2019-2021 (Grant-in-Aid): Establishing an in vivo humanised mouse model for telomere related Bone Marrow Failure Syndromes. Professor Tracy Bryan, Children’s Medical Research Institute.

Human genetic information is packaged into discrete bundles (chromosomes) that have protective caps on their ends, known as ‘telomeres’. The integrity of telomeres is vitally important for cells to continue to divide. A subset of inherited Bone Marrow Failure Syndromes, known as Telomere Biology Disorders, are caused by mutations in genes that are responsible for protecting telomeres. In these patients, degraded telomeres lead to the premature death of cells in the bone marrow, resulting in bone marrow failure.

The goal of this study is to use the latest developments in gene editing of human bone marrow cells to establish a mouse model that closely mimics the disease process in human Telomere Biology Disorders. This model will be used for determining how particular patient mutations cause disease, thus providing a more precise molecular diagnosis for patients and their families, and for creation of a platform to test potential new gene therapy cures for this form of inherited bone marrow failure.