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 genet ic demyelinating disease caused by a mutation of the galactosylceramidase g ene. Demyelination of the central nervous system commences around 20 postna tal days. Using GFP-transgenic mice as donors, the distribution of hematoge nous cells after bone marrow transplantation was investigated in the twitch er mice. Bone marrow transplantation was carried out at 8 postnatal days. I n twitcher chimeric mice examined before 30 postnatal days, numerous GFP(+) cells were detected in spleen and peripheral nerve but only a few were det ected in the liver, lung, and spinal white matter. In contrast, at 35 to 40 postnatal days when demyelination is evident, many GFP(+) cells with amebo id form were detected in the white matter of the spinal cord, brainstem, an d cerebrum, Approximately half of these GFP(+) cells were co-labeled with M ac-1. In twitcher chimeric mice examined after 100 postnatal days, the majo rity of GFP/Mac-1 double-positive cells displayed the morphological feature s of ramified microglia with fine delicate processes and was distributed di ffusely in both gray and white matter. These results suggest that a signifi cant number of donor hematogenous cells are able to infiltrate into the bra in parenchyma, repositioning themselves into areas previously occupied by m icroglia, and to ameliorate lethality.