title: Bone Marrow Transplantation Alters the Tremor Phenotype in the Murine Model of Globoid-Cell Leukodystrophy.
abstract: 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 revealed. Results showed that twitcher mice had significantly increased power across a broad band of higher frequencies compared to wildtype mice. Bone marrow transplantation (BMT), the only available therapy for GLD, worsened the tremor in the twitcher mice and induced a measureable alteration of movement phenotype in the wildtype mice. These data highlight the damaging effects of conditioning radiation and BMT in the neonatal period. The behavioral methodology used herein provides a quantitative approach for assessing the efficacy of potential therapeutic interventions for Krabbe's disease.
authors.affiliation: Department of Internal Medicine, Campus box 8007, 660 South Euclid Avenue, Washington University School of Medicine, St. Louis, MO 63110, USA.
authors.forename: Adarsh S
authors.initials: AS
authors.lastname: Reddy
authors.forename: David F
authors.initials: DF
authors.lastname: Wozniak
authors.forename: Nuri B
authors.initials: NB
authors.lastname: Farber
authors.forename: Joshua T
authors.initials: JT
authors.lastname: Dearborn
authors.forename: Stephen C
authors.initials: SC
authors.lastname: Fowler
authors.forename: Mark S
authors.initials: MS
authors.lastname: Sands
keywords: bone marrow transplantation; galactosylceramidase; globoid-cell leukodystrophy; lysosomal storage disease; tremor