Tremor is a prominent phenotype of the twitcher mouse, an authentic genetic model of Globoid-Cell Leukodystrophy (GLD, Krabbe's disease). In the current study, the tremor was quantified using a force-plate actometer designed to accommodate low-weight mice. The actometer records the force oscillations caused by a mouse's movements, and the rhythmic structure of the force variations can be reveal...

One of the most exciting aspects of modern cell biology is the potential to make connections between disparate areas of research, and thus open up new lines of enquiry. Two recent papers have done just this (Kanazawa et al., 2000; Im et al., 2001, this issue). Building on the biochemical defect in an inherited metabolic disease (Suzuki, 1998), these papers reveal an unexpected connection betwee...

One of the most exciting aspects of modern cell biology is the potential to make connections between disparate areas of research, and thus open up new lines of enquiry. Two recent papers have done just this (Kanazawa et al., 2000; Im et al., 2001, this issue). Building on the biochemical defect in an inherited metabolic disease (Suzuki, 1998), these papers reveal an unexpected connection betwee...

Leukoencephalopathies are diseases with high clinical heterogeneity. In clinical work, it's difficult for doctors to make a definite etiological diagnosis. Here, we designed a custom probe library which contains the known pathogenic genes reported to be associated with Leukoencephalopathies, and performed targeted gene capture and massively parallel sequencing (MPS) among 49 Chinese patients wh...

Krabbe disease (KD) (globoid cell leukodystrophy) is a degenerative, lysosomal storage disease, caused by a severe loss of galactocerebrosidase (GALC) enzymatic activity. The inheritance is autosomal recessive. KD affects the white matter of the central and peripheral nervous systems. We present a 3 year old boy in whom the disease had an 'infantile' or 'classic' presentation, with spasticity, ...

The Twitcher mouse (twi/twi) has been widely used as an animal model of globoid cell leukodystrophy (GLD; Krabbe disease), a hereditary leukodystrophy due to genetic galactosylceramidase deficiency. Recently, we generated a new mouse model of late-onset, chronic GLD (SAP-A-/- mice) by introducing a mutation (C106F) in the saposin A domain of the sphingolipid activator protein gene. Comparative ...

Natural killer (NK) cells exert important immunoregulatory functions by releasing several inflammatory molecules, such as IFN-γ and members of chemokines, which include CCL3/MIP-1α and CCL4/MIP-1β. These cells also express heptahelical receptors, which are coupled to heterotrimeric G proteins that guide them into inflamed and injured tissues. NK cells have been shown to recognize and destroy tr...

Copyright © 2010 Frederick Furness Publishing 16 A focus on enzyme replacement therapies (ERT) for lysosomal storage diseases has led Shire Human Genetic Therapies, Inc (Shire HGT) to develop products for treating Fabry disease, Hunter syndrome, and type 1 Gaucher disease. These products are administered intravenously (IV) and are effective in treating the somatic symptoms of the disease. Devel...