Distribution and characterization of GFP+ donor hematogenous cells in twitcher mice after bone marrow transplantation

Yun Ping Wu, Eileen McMahon, Meredith R. Kraine, Roland Tisch, Anthony Meyers, Jeffrey Frelinger, Glenn K. Matsushima, Kinuko Suzuki

Research output: Contribution to journalArticle

57 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1849-1854
Number of pages6
JournalAmerican Journal of Pathology
Volume156
Issue number6
DOIs
StatePublished - Jan 1 2000
Externally publishedYes

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

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