Publication Date:
1988-02-26
Description:
The twitcher mouse is an animal model of galactosylceramidase deficiency, comparable to Krabbe's disease, a lysosomal storage disease in humans. As in most lysosomal storage diseases, neurological deterioration is a prominent feature of the disease in these mice. Transplantation of enzymatically normal congenic bone marrow was earlier found to result in prolonged survival and increased levels of galactosylceramidase in the visceral organs of twitcher mice. It is now reported that bone marrow transplantation results in increased galactosylceramidase levels in the central nervous system (CNS). Concomitantly, the levels of psychosine, a highly toxic lipid that progressively accumulates in the CNS of untreated twitcher mice, stabilized at much lower levels in the CNS of treated twitcher mice. Histologically, a gradual disappearance of globoid cells, the histological hallmark of Krabbe's disease, and the appearance of foamy macrophages capable of metabolizing the storage product were seen in the CNS. By immunohistochemical labeling it was demonstrated that these foamy macrophages were of donor origin. The infiltration of enzymatically competent, donor-derived macrophages was accompanied by extensive remyelination in the CNS. It is concluded that after bone marrow transplantation, donor-derived macrophages infiltrate the affected brain tissue and are capable of inducing a partial reversal of the enzyme deficiency.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Hoogerbrugge, P M -- Suzuki, K -- Poorthuis, B J -- Kobayashi, T -- Wagemaker, G -- van Bekkum, D W -- HD 03110/HD/NICHD NIH HHS/ -- NS 24453/NS/NINDS NIH HHS/ -- NS 24928/NS/NINDS NIH HHS/ -- New York, N.Y. -- Science. 1988 Feb 26;239(4843):1035-8.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Pediatrics, University Hospital, Leiden, The Netherlands.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/3278379" target="_blank"〉PubMed〈/a〉
Keywords:
Animals
;
Bone Marrow/enzymology/immunology
;
*Bone Marrow Transplantation
;
Brain/*enzymology/pathology
;
Cerebellum/pathology
;
Galactosidases/*deficiency
;
Galactosylceramidase/*deficiency/metabolism
;
H-2 Antigens/analysis
;
Immunohistochemistry
;
Leukodystrophy, Globoid Cell/enzymology/pathology/therapy
;
Macrophages/enzymology/*transplantation
;
Mice
;
Mice, Inbred C57BL
;
Mice, Neurologic Mutants
;
Microscopy, Electron
;
Myelin Sheath/pathology
;
Psychosine/metabolism
;
Spinal Cord/*enzymology/pathology
Print ISSN:
0036-8075
Electronic ISSN:
1095-9203
Topics:
Biology
,
Chemistry and Pharmacology
,
Computer Science
,
Medicine
,
Natural Sciences in General
,
Physics
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