The twitcher mouse: accumulation of galactosylsphingosine and pathology of the sciatic nerve
References (19)
- et al.
Inhibition of cytochrome c oxidase by psychosine (galactosylsphingosine)
Biochem. Biophys. Res. Commun.
(1986) - et al.
The pathogenesis of globoid cell leucodystrophy in peripheral nerve of the mouse mutant twitcher
J. Neurol. Sci.
(1982) - et al.
The twitcher mouse: an enzymatically authentic model of human globoid cell leukodystrophy (Krabbe disease)
Brain Research
(1980) - et al.
The twitcher mouse: determination of genetic status by galactosylceramidase assays on clipped tail
Biochem. Med.
(1982) - et al.
Globoid cell leukodystrophy is a generalized galactosylsphingosine (psychosine) storage disease
Biochem. Biophys. Res. Commun.
(1987) - et al.
Globoid cell leukodystrophy: additional deficiency of psychosine galactosidase
Biochem. Biophys. Res. Commun.
(1972) - et al.
The twitcher mouse: normal pattern of early myelination in the spinal cord
Brain Research
(1982) - et al.
The twitcher mouse: Degeneration of oligodendrocytes in vitro
Dev. Brain Res.
(1986) - et al.
Krabbe disease: a galactosylsphingosine (psychosine) lipidosis
J. Lipid Res.
(1980)
Cited by (56)
Early axonal loss accompanied by impaired endocytosis, abnormal axonal transport, and decreased microtubule stability occur in the model of Krabbe's disease
2014, Neurobiology of DiseaseCitation Excerpt :In these animals, a dying-back neuropathy has been proposed, since apoptosis of motor neurons develops later, while in the sciatic nerve, distal axonal defects are already evident before myelin loss occurs (Castelvetri et al., 2011). Despite the presence of axonopathy, there is still conflicting evidence as to axonal loss in Twitcher nerves (Jacobs et al., 1982; Kobayashi et al., 1988; Tanaka et al., 1988). The characterization of axonal pathology in KD is still limited, and its understanding is of great interest since therapies devised for this disorder, including enzyme replacement therapy, gene therapy and cell transplantation aim mainly at targeting myelinating cells whereas neuroprotective strategies have been neglected.
Late-onset Krabbe disease is predominant in Japan and its mutant precursor protein undergoes more effective processing than the infantile-onset form
2014, GeneCitation Excerpt :GALC enzymatic activity is predominantly targeted in lysosomes, where it is essential for normal catabolism of galactolipids, including a major myelin component, galactocerebroside, and psychosine. GALC deficiency results in abnormal accumulation of galactosylsphingosine (psychosine), which is cytotoxic to oligodendrocytes and Schwann cells (Nagara et al., 1986; Tanaka et al., 1988). Loss of these myelin-forming cells causes demyelination in both the central and peripheral nervous systems during early developmental stages (Kobayashi et al., 1988; Seitelberger, 1981).
Factors that affect postnatal bone growth retardation in the twitcher murine model of Krabbe disease
2010, Biochimica et Biophysica Acta - Molecular Basis of DiseaseMulti-system disorders of glycosphingolipid and ganglioside metabolism
2010, Journal of Lipid ResearchCitation Excerpt :In V394L/SapC−/− mice, increased glucosylsphingosine is present by 14 days, i.e., before the onset of neurological signs at 30 days (Table 1). Abnormal accumulation of galactosylsphingosine in twitcher mice is detected in the brain and sciatic nerves at postnatal day 7, before the onset of demyelination, and progressively increases to 100-fold normal levels, predominantly in white matter (209, 210). In normal mice, GM2 is not detectable, but GM2 is elevated at postnatal day 2 in Sandhoff mice before any pathological signs (171).
Globoid Cell Leukodystrophy (Krabbe Disease): An Update
2023, ImmunoTargets and Therapy