A gene that allows mice to accept human bone marrow cells more efficiently is presented online in Nature Immunology. The gene, called Sirpa, limits graft failure of transplanted blood stem cells and was found by studying different strains of immunodeficient mice that varied in their ability to accept human blood stem cell transplants.
Such mice serve as valuable tools to study human blood cell deficiencies or diseases. That closely related inbred mouse strains showed differences in engraftment frequencies quickly narrowed the search for the gene. The mouse Sirpa genes are polymorphic, meaning that stable inherited differences are found in these genes that can alter their function.
The protein encoded by Sirpa, SIRP-alpha, interacts with another protein called CD47 expressed on the surface of the human blood cells. This interaction is thought to prevent a class of immune scavenging cells called phagocytes from attacking and eating cells that lack CD47 or have CD47 molecules that cannot be recognized by SIRP-alpha. This latter possibility is why some mouse strains rejected their human blood transplant while other strains did not.
These differences, however, are not restricted to mice. Humans likewise display polymorphisms in the human SIRPA gene. The authors speculate such differences might explain why some bone marrow transplants are rejected despite being 'tissue matched' by other criteria for donor-recipient compatibility. If correct, SIRPA can be added to this list of markers used to screen for suitable donors to make bone marrow transplant safer and more successful.
Jayne S Danska (Hospital for Sick Children, Toronto, ON, Canada)
Abstract available online.
(C) Nature Immunology press release.
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