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.
Keywords
To read this article in full you will need to make a payment
Purchase one-time access:
Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online accessOne-time access price info
- For academic or personal research use, select 'Academic and Personal'
- For corporate R&D use, select 'Corporate R&D Professionals'
Subscribe:
Subscribe to Journal of the Neurological SciencesAlready a print subscriber? Claim online access
Already an online subscriber? Sign in
Register: Create an account
Institutional Access: Sign in to ScienceDirect
References
- Chromosomal mapping of mouse myelin basic protein gene and structure and transcription of the partially deleted gene in shiverer mutant mice.Cell. 1985; 42: 149-155
- Shiverer: an autosomal recessive mutant mouse with myelin deficiency.J Hered. 1981; 72: 128
- Expression of a myelin basic protein gene in transgenic shiverer mice: correction of the dysmyelinating phenotype.Cell. 1987; 48: 703-712
- Towards the reconstruction of central nervous system white matter using neural precursor cells.Brain. 2001; 124: 2147-2161
- Oligodendrocytes and stem cell transplantation: their potential in the treatment of leukoencephalopathies.J Inherit Metab Dis. 2005; 28: 357-368
- Glial progenitor-based repair of demyelinating neurological diseases.Neurosurg Clin N Am. 2007; 18: 93-104
- Demyelinating diseases and potential repair strategies.Int J Dev Neurosci. 2007; 25: 149-153
- Myelination of congenitally dysmyelinated spinal cord axons by adult neural precursor cells results in formation of nodes of Ranvier and improved axonal conduction.J Neurosci. 2007; 27: 3416-3428
- Human oligodendrocytes derived from embryonic stem cells: effect of noggin on phenotypic differentiation in vitro and on myelination in vivo.Mol Cell Neurosci. 2007; 34: 310-323
- “Global” cell replacement is feasible via neural stem cell transplantation: evidence from the dysmyelinated shiverer mouse brain.Proc Natl Acad Sci USA. 1999; 96: 7029-7034
- Motor function analysis of myelin mutant mice using a rotarod.Int J Dev Neurosci. 1995; 13: 715-722
- Neonatal chimerization with human glial progenitor cells can both remyelinate and rescue the otherwise lethally hypomyelinated shiverer mouse.Cell Stem Cell. 2008; 2: 553-565
- Alteration of the primary pattern of central myelin in a chimaeric environment — study of shiverer ↔ wild-type chimaeras.Dev Brain Res. 1986; 26: 239-247
- Disruption of Ini1 leads to peri-implantation lethality and tumorigenesis in mice.Mol Cell Biol. 2001; 21: 3598-3603
- Rapid preimplantation detection of mutant (shiverer) and normal alleles of the mouse myelin basic protein gene allowing selective implantation and birth of live young.Proc Natl Acad Sci USA. 1990; 87: 4481-4484
- Hof P.R. Young W.G. Bloom F.E. Belichenko P.V. Celio M.R. Comparative Cytoarchitectonic Atlas of the C57BL/6 and 129/Sv Mouse Brains. Elsevier Science BV, Amsterdam2000
- Rescue of cardiac defects in Id knockout embryos by injection of embryonic stem cells.Science. 2004; 306: 247-252
- Rescue of morphogenetic defects and of retinoic acid signaling in retinaldehyde dehydrogenase 2 (Raldh2) mouse mutants by chimerism with wild-type cells.Differentiation. 2006; 74: 661-668
- Myelin deficient mice: expression of myelin basic protein and generation of mice with varying levels of myelin.Cell. 1987; 48: 713-721
- Morphometric analysis of normal, mutant, and transgenic CNS: correlation of myelin basic protein expression to myelinogenesis.J Neurochem. 1992; 58: 342-349
- Axoglial junctions in the mouse mutant shiverer.Brain Res. 1981; 208: 283-297
- Hypomyelination alters K+ channel expression in mouse mutants shiverer and trembler.Neuron. 1995; 15: 1337-1347
- Dependence of nodal sodium channel clustering on paranodal axoglial contact in the developing CNS.J Neurosci. 1999; 19: 7516-7528
- Formation of compact myelin is required for maturation of the axonal cytoskeleton.J Neurosci. 1999; 19: 7278-7288
Article info
Publication history
Accepted:
September 17,
2008
Received in revised form:
September 2,
2008
Received:
March 13,
2008
Identification
Copyright
© 2008 Elsevier B.V. Published by Elsevier Inc. All rights reserved.
