Disease relevance of Leukodystrophy, Globoid Cell

• The twitcher mouse is an animal model of galactosylceramidase deficiency (Krabbe's disease), a human sphingolipidosis [1].
• Normal or near normal levels of all saposins were found in patients with Krabbe disease, metachromatic leukodystrophy, Fabry disease, adrenoleukodystrophy, I-cell disease, mucopolysaccharidosis types 2 and 3B, or Jansky-Bielschowsky disease [2].
• Twitcher (twi/twi) is a murine model of a human genetic demyelinating disease, globoid cell leukodystrophy (Krabbe disease) [3].
• Globoid cell leukodystrophy (Krabbe disease) is an autosomal recessive inherited neurodegenerative disorder caused by the deficiency of the lysosomal enzyme beta-galactosylceramidase [4].
• METHODS: Concentrated retrovirus encoding the LacZ gene was injected into the cerebral ventricles of the embryos of normal and twitcher mice (a murine model of Krabbe disease) at embryonic day 12 [5].

Psychiatry related information on Leukodystrophy, Globoid Cell

• METHODS: Brain CT and/or MR studies were done in 57 children 3 to 36 months of age: 16 with infantile neuronal ceroid lipofuscinosis, 5 with Rett syndrome, 6 with Krabbe disease, and 30 control subjects with normal neurologic status [6].

High impact information on Leukodystrophy, Globoid Cell

• The twitcher mouse is a mutant affected by a form of leukodystrophy which shows close similarities to human globoid cell (Krabbe's) leukodystrophy [7].
• 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 [8].
• The gene responsible for Krabbe disease, an autosomal recessive disorder caused by deficiency of galactocerebrosidase (GALC), was localized by multipoint linkage analysis on chromosome 14 [9].
• Adult-onset Krabbe's disease in siblings with novel mutations in the galactocerebrosidase gene [10].
• Globoid cell leukodystrophy (GLD) or Krabbe disease is an autosomal recessively inherited neurological disease caused by mutations in the gene coding for the lysosomal enzyme galacto-cerebrosidase (GALC) [11].

Chemical compound and disease context of Leukodystrophy, Globoid Cell

• Fabry's disease patients showed an increase in globotriaosylceramide, but Krabbe's disease patients did not demonstrate an increase in galactosylceramide [12].
• 1. Psychosine (beta-galactosylsphingosine) is the toxic agent in Krabbe's disease (globoid cells leukodystrophy) [13].
• Human brain cerebroside beta-galactosidase: deficiency of transgalactosidic activity in Krabbe's disease [14].
• Therefore, the accumulation of lysosulfatide may explain the demyelination in patients with MLD, as is the case with Krabbe disease [15].
• Galactosylsphingosine has previously been shown to be neurotoxic in globoid cell leukodystrophy (Krabbe disease) [16].

Biological context of Leukodystrophy, Globoid Cell

• We investigated whether up-regulation of L-PGDS is either unique to Krabbe's disease or is a more generalized phenomenon in lysosomal storage disorders (LSDs), using LSD mouse models of Tay-Sachs disease, Sandhoff disease, GM(1) gangliosidosis and Niemann-Pick type C1 disease [17].
• The expression of the major histocompatibility complex Class I antigens (Class I) was investigated in the nervous system of twitcher (C57BL/6J-twi), a murine model of Krabbe disease in humans [18].
• Galactosylsphingosine hydrolysis was also deficient in cell homogenates from Krabbe's disease (beta-galactocerebrosidase-deficient) patients, but not acid beta-galactosidase-deficient patients [19].
• In 24 pregnancies at risk for Krabbe disease (KD) monitored by amniocentesis in the 15th to 18th week, the amniocytic galactosyl ceramide beta-galactosidase activity was either lower than 11% (n = 12) or higher than 28% (n = 12) of the mean control amniocytic activity (n = 27) [20].

Anatomical context of Leukodystrophy, Globoid Cell

• The effect of allogeneic bone marrow transplantation (BMT) was investigated in the neurologically affected twitcher mouse, a model for human Krabbe's disease [21].
• The residual galactosylceramide beta-galactosidase activity in cultured skin fibroblasts from a child with late-onset globoid cell leukodystrophy (GLD) was distinctly different from that found in the typical infantile form of the disease [22].
• The percentage of membrane-bound carbonic anhydrase was lower than normal in white matter from Krabbe disease and adrenoleukodystrophy; isolated myelin had a low specific activity in these diseases [23].
• L-PGDS is expressed in oligodendrocytes (OLs) in the central nervous system and is up-regulated in OLs of the twitcher mouse, a model of globoid cell leukodystrophy (Krabbe's disease) [17].
• Psychosine was isolated also from the cerebral cortex in Psychosine was isolated also from the cerebral cortex in Krabbe disease after derivatization to the N-acetyl form [24].

Gene context of Leukodystrophy, Globoid Cell

• Globoid cell leukodystrophy (Krabbe disease) is an autosomal recessive disorder resulting from the deficiency of galactocerebrosidase (GALC) activity [25].
• The expression of IL-6 is greatly enhanced in the twitcher mouse (S. M. LeVine and D. C. Brown, 1997, J. Neuroimmunol. 73, 47-56), which is an authentic animal model of globoid cell leukodystrophy (Krabbe's disease) [26].
• Using magnetic resonance (MR) diffusion-weighted method, we examined the optic and the trigeminal nerves of jimpy and twitcher mice, considered to be animal models of Pelizaeus-Merzbacher disease, hypomyelination disorder, and Krabbe disease, demyelination disorder, respectively [27].
• Hematopoietic stem cell transplantation has proven to have a positive effect on the course of some patients with late-onset Krabbe disease [28].
• Modifier genes may account for the phenotypic variability observed in the late-onset forms of globoid cell leukodystrophy (GCL) in humans [29].

Analytical, diagnostic and therapeutic context of Leukodystrophy, Globoid Cell

• The twitcher mouse: a model for Krabbe disease and for experimental therapies [30].
• Molecular cloning and expression of cDNA for murine galactocerebrosidase and mutation analysis of the twitcher mouse, a model of Krabbe's disease [31].
• Clinical and cerebral FDG PET scan in a patient with Krabbe's disease [32].
• For gene therapy to the CNS, a recombinant adenovirus encoding beta-galactocerebrosidase gene was injected into the cerebral ventricle of neonatal twitcher mice, a murine model of Krabbe disease [33].

References