Distribution and characterization of GFP(+) donor hematogenous cells in Twitcher mice after bone marrow transplantation.
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.
Wu
Y P
YP
Department of Pathology and Laboratory Medicine, the University of North Carolina, Chapel Hill 27599-7525, USA.
McMahon
E
E
Kraine
M R
MR
Tisch
R
R
Meyers
A
A
Frelinger
J
J
Matsushima
G K
GK
Suzuki
K
K
D000818:Animals; D001773:Blood Cells / Q000378:metabolism / Q000637:transplantation*; D016026:Bone Marrow Transplantation; D002490:Central Nervous System / Q000378:metabolism; D049452:Green Fluorescent Proteins; D007202:Indicators and Reagents; D008164:Luminescent Proteins / Q000097:blood / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D008818:Mice, Neurologic Mutants; D008822:Mice, Transgenic; D010525:Peripheral Nerves / Q000378:metabolism; D011182:Postoperative Care; D012016:Reference Values; D014018:Tissue Distribution; D014019:Tissue Donors; D014781:Viscera / Q000378:metabolism
D007202:Indicators and Reagents; D008164:Luminescent Proteins; D049452:Green Fluorescent Proteins