title: Embryonic stem cell rescue of tremor and ataxia in myelin-deficient shiverer mice.
abstract: Transplantation of neural precursor cells has been proposed as a possible approach for replacing missing or damaged central nervous system myelin. Neonatal and adult myelin-deficient shiverer (shi) mice, bearing a mutation of the myelin basic protein (MBP) gene, have been used extensively as hosts for testing cell engraftment, migration, and myelination, but relatively little progress has been made in reversing shi motor deficits. Here we describe a prenatal cell replacement strategy, showing that embryonic stem cells injected into shi blastocyst embryos can generate chimeric mice with strong and widespread immunoreactive MBP expression throughout the brain and a behavioral (motor) phenotype that appears essentially rescued.
authors.affiliation: Department of Neurology, University of Massachusetts Medical School, Worcester, MA 01655, USA. hoipang.low@umassmed.edu
authors.forename: Hoi Pang
authors.initials: HP
authors.lastname: Low
authors.forename: Béatrice
authors.initials: B
authors.lastname: Gréco
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Tanahashi
authors.forename: Judith
authors.initials: J
authors.lastname: Gallant
authors.forename: Stephen N
authors.initials: SN
authors.lastname: Jones
authors.forename: Susan
authors.initials: S
authors.lastname: Billings-Gagliardi
authors.forename: Lawrence D
authors.initials: LD
authors.lastname: Recht
authors.forename: William J
authors.initials: WJ
authors.lastname: Schwartz
mesh_terms: D000818:Animals; D001259:Ataxia / Q000209:etiology* / Q000601:surgery*; D051792:Basic Helix-Loop-Helix Proteins / Q000378:metabolism; D003711:Demyelinating Diseases / Q000150:complications* / Q000235:genetics / Q000473:pathology; D004622:Embryo, Mammalian; D053595:Embryonic Stem Cells / Q000637:transplantation*; D005838:Genotype; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D051379:Mice; D008818:Mice, Neurologic Mutants; D009154:Mutation; D004676:Myelin Basic Protein / Q000235:genetics; D010751:Phosphopyruvate Hydratase / Q000378:metabolism; D014202:Tremor / Q000209:etiology* / Q000628:therapy*
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D005904:Glial Fibrillary Acidic Protein; D004676:Myelin Basic Protein; D010751:Phosphopyruvate Hydratase; C494786:Olig1 protein, mouse