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(American Journal of Pathology. 2000;156:1849-1854.)
© 2000 American Society for Investigative Pathology

Short Communications

Distribution and Characterization of GFP+ Donor Hematogenous Cells in Twitcher Mice after Bone Marrow Transplantation

Yun-Ping Wu*, Eileen McMahon{dagger}, Meredith R. Kraine{dagger}, Roland Tisch{dagger}, Anthony Meyers{ddagger}, Jeffrey Frelinger{dagger}, Glenn K. Matsushima{dagger}§¶ and Kinuko Suzuki*§

From the Departments of Pathology and Laboratory Medicine,*
Microbiology and Immunology,{dagger}
and Surgery,{ddagger}
the Neuroscience Center,§
and the Program for Molecular Biology of Biotechnology,
the University of North Carolina, Chapel Hill, North Carolina

The twitcher mouse is a murine model of globoid cell leukodystropy, a genetic demyelinating disease caused by a mutation of the galactosylceramidase gene. Demyelination of the central nervous system commences around 20 postnatal days. Using GFP-transgenic mice as donors, the distribution of hematogenous cells after bone marrow transplantation was investigated in the twitcher mice. Bone marrow transplantation was carried out at 8 postnatal days. In twitcher chimeric mice examined before 30 postnatal days, numerous GFP+ cells were detected in spleen and peripheral nerve but only a few were detected in the liver, lung, and spinal white matter. In contrast, at 35 to 40 postnatal days when demyelination is evident, many GFP+ cells with ameboid form were detected in the white matter of the spinal cord, brainstem, and cerebrum. Approximately half of these GFP+ cells were co-labeled with Mac-1. In twitcher chimeric mice examined after 100 postnatal days, the majority of GFP/Mac-1 double-positive cells displayed the morphological features of ramified microglia with fine delicate processes and was distributed diffusely in both gray and white matter. These results suggest that a significant number of donor hematogenous cells are able to infiltrate into the brain parenchyma, repositioning themselves into areas previously occupied by microglia, and to ameliorate lethality.




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