Human blood proteins produced by mice
26th January 2006
Researchers have developed a new genetically modified mouse to help them study the genetic blood condition, alpha thalassemia. The disorder causes some carriers to be severely anaemic, a condition that makes people pale and listless. This mouse model will enable scientists to better understand how alpha-thalassemia affects people and figure out how the gene that instructs the body to make alpha-globin normally works.
People who have alpha-thalassemia have a shortage of the protein alpha-globin which is a crucial component of the oxygen-carrying molecule haemoglobin in red blood cells. As a result they lack haemoglobin which means their red blood cells cannot carry enough oxygen around the body. It is most common in people of African, Middle Eastern, Indian, Southeast Asian and southern Chinese descent.
The scientists created mice that produce the human form of a blood protein called alpha-globin. They achieved this by removing the mouse gene for alpha-globin from the stem cells of a mouse embryo and replacing it with a copy of the human gene. Because this transfer happened at such an early stage in development, when the mice were born they produced the human form of alpha-globin, rather than the mouse version.
The new mouse model was developed by researchers at the Medical Research Council’s Molecular Haematology Unit (MHU) in Oxford and Edinburgh University’s Institute for Stem Cell Research.
To insert the human gene into mouse DNA, the team developed a new technique called recombinase-mediated genomic replacement (RMGR) that allowed them to replace large segments of the mouse genome with the equivalent human region. Because the alpha-globin cluster of genes has been fully compared in mouse and man, they chose this section of DNA to test the RMGR technique.
Professor Doug Higgs, Director of the MHU, explained the RMGR technique’s advantage:
“At present a great deal of our understanding of human genetics relies on mouse models. However, such models do not always faithfully mimic the situation in humans. This work represents an important step forward in producing more authentic models of human genetic disease.”
He continued: ‘‘Scientists may be able to apply this technique to other genes to create mouse-models of genetic conditions that affect human health. The knowledge gained from studying these mice could also be used to develop new treatments.’’
Original Research Paper:
Wallace, H.A.C., Marques-Kranc, F., Richardson, M., Luna-Crespo, F.,
Sharpe, J.A., Hughes, J., Wood, W.G., Higgs, G.R and Smith, A.J.H. Manipulating the mouse genome to engineer precise functional syntenic
replacements with human sequence. Cell (2007) 128: 197-209.
