New Mouse Model Successfully Created for the Study of Aplastic Anemia

A transgenic mouse model simulating human aplastic anemia has been created and it was used in a study identifying a molecular process linking the bone marrow failure in the disease with telomere impairment.

Some patients of aplastic anemia (characterized by a reduced number of bone marrow cells that differentiate into the various blood cell types) have been found to have genetic alterations leading to a shortening of their telomeres. The repetitive DNA sequence of telomeres is bound to a set of proteins, which guards against telomere degradation and/or damage. Using transgenic methods, a scientific team at the Spanish National Cancer Research Centre (CNIO; Madrid, Spain) has succeeded in eliminating one of these proteins, Trf1, from mouse bone marrow in order to explore its role in the tissue's function. The researchers discovered that when Trf1 is eliminated the mice develop the same symptoms that characterize human aplastic anemia sufferers: bone marrow failure with the corresponding pancytopenia (reduction in the number of red and white blood cells, and platelets). The authors also showed, for the first time, that the absence of this protein causes a shortening of the telomeres of blood cell-producing stem cells, which leads in turn to the progressive stress-induced death of the remaining stem cells in the tissue and, eventually, the death of the animal.


This discovery, published August 29, 2012, in the online edition of the journal Blood, establishes the molecular bases of certain genetic variants of aplastic anemia and opens a new line of attack via Trf1 to help prevent the telomere shortening and cell death that trigger the disease. "We have generated an animal model for aplastic anemia associated with short telomeres that may aid in the design and testing of new therapeutic strategies," said study leader Dr. Maria Blasco. These findings may also offer insights into other processes linked to telomere length, such as ageing and cancer.

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Centro Nacional de Investigaciones Oncologicas (CNIO)