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Defective oligodendrocyte development and severe hypomyelination in PDGF-A knockout mice.

Fruttiger, M.; Karlsson, L.; Hall, A. C.; Abramsson, A.; Calver, A. R.; Ehrencrona, Hans LU ; Willetts, K.; Bertold, C. H.; Heath, J. K. and Betsholtz, C., et al. (1999) In Development 126(3). p.457-467
Abstract
There is a class of oligodendrocyte progenitors, called O-2A progenitors, that is characterized by expression of platelet-derived growth factor &agr;-receptors (PDGFR(&agr;)). It is not known whether all oligodendrocytes are derived from these PDGFRalpha-progenitors or whether a subset(s) of oligodendrocytes develops from a different, PDGFR alpha-negative lineage(s). We investigated the relationship between PDGF and oligodendrogenesis by examining mice that lack either PDGF-A or PDGF-B. PDGF-A null mice had many fewer PDGFR alpha-progenitors than either wild-type or PDGF-B null mice, demonstrating that proliferation of these cells relies heavily (though not exclusively) on PDGF-AA homodimers. PDGF-A-deficient mice also had reduced... (More)
There is a class of oligodendrocyte progenitors, called O-2A progenitors, that is characterized by expression of platelet-derived growth factor &agr;-receptors (PDGFR(&agr;)). It is not known whether all oligodendrocytes are derived from these PDGFRalpha-progenitors or whether a subset(s) of oligodendrocytes develops from a different, PDGFR alpha-negative lineage(s). We investigated the relationship between PDGF and oligodendrogenesis by examining mice that lack either PDGF-A or PDGF-B. PDGF-A null mice had many fewer PDGFR alpha-progenitors than either wild-type or PDGF-B null mice, demonstrating that proliferation of these cells relies heavily (though not exclusively) on PDGF-AA homodimers. PDGF-A-deficient mice also had reduced numbers of oligodendrocytes and a dysmyelinating phenotype (tremor). Not all parts of the central nervous system (CNS) were equally affected in the knockout. For example, there were profound reductions in the numbers of PDGFR alpha-progenitors and oligodendrocytes in the spinal cord and cerebellum, but less severe reductions of both cell types in the medulla. This correlation suggests a close link between PDGFRalpha-progenitors and oligodendrogenesis in most or all parts of the CNS. We also provide evidence that myelin proteolipid protein (PLP/DM-20)-positive cells in the late embryonic brainstem are non-dividing cells, presumably immature oligodendrocytes, and not proliferating precursors. (Less)
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published
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keywords
Proto-Oncogene Proteins, Platelet-Derived Growth Factor, Oligodendroglia, Myelin Sheath, Myelin Proteolipid Protein, Knockout, Mice, Central Nervous System, Cell Division, Cell Differentiation, Animals, Brain, Proto-Oncogene Proteins c-sis, Receptor, Platelet-Derived Growth Factor alpha, Receptors
in
Development
volume
126
issue
3
pages
457 - 467
publisher
Society for International Development
external identifiers
  • scopus:0033031266
ISSN
1477-9129
language
English
LU publication?
no
id
a67b8b71-b2d4-44e0-986d-13189e8e931c (old id 4021975)
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http://www.ncbi.nlm.nih.gov/pubmed/9876175
date added to LUP
2013-10-21 10:52:15
date last changed
2017-10-29 04:28:16
@article{a67b8b71-b2d4-44e0-986d-13189e8e931c,
  abstract     = {There is a class of oligodendrocyte progenitors, called O-2A progenitors, that is characterized by expression of platelet-derived growth factor &agr;-receptors (PDGFR(&agr;)). It is not known whether all oligodendrocytes are derived from these PDGFRalpha-progenitors or whether a subset(s) of oligodendrocytes develops from a different, PDGFR alpha-negative lineage(s). We investigated the relationship between PDGF and oligodendrogenesis by examining mice that lack either PDGF-A or PDGF-B. PDGF-A null mice had many fewer PDGFR alpha-progenitors than either wild-type or PDGF-B null mice, demonstrating that proliferation of these cells relies heavily (though not exclusively) on PDGF-AA homodimers. PDGF-A-deficient mice also had reduced numbers of oligodendrocytes and a dysmyelinating phenotype (tremor). Not all parts of the central nervous system (CNS) were equally affected in the knockout. For example, there were profound reductions in the numbers of PDGFR alpha-progenitors and oligodendrocytes in the spinal cord and cerebellum, but less severe reductions of both cell types in the medulla. This correlation suggests a close link between PDGFRalpha-progenitors and oligodendrogenesis in most or all parts of the CNS. We also provide evidence that myelin proteolipid protein (PLP/DM-20)-positive cells in the late embryonic brainstem are non-dividing cells, presumably immature oligodendrocytes, and not proliferating precursors.},
  author       = {Fruttiger, M. and Karlsson, L. and Hall, A. C. and Abramsson, A. and Calver, A. R. and Ehrencrona, Hans and Willetts, K. and Bertold, C. H. and Heath, J. K. and Betsholtz, C. and Richardson, W. D.},
  issn         = {1477-9129},
  keyword      = {Proto-Oncogene Proteins,Platelet-Derived Growth Factor,Oligodendroglia,Myelin Sheath,Myelin Proteolipid Protein,Knockout,Mice,Central Nervous System,Cell Division,Cell Differentiation,Animals,Brain,Proto-Oncogene Proteins c-sis,Receptor,Platelet-Derived Growth Factor alpha,Receptors},
  language     = {eng},
  number       = {3},
  pages        = {457--467},
  publisher    = {Society for International Development},
  series       = {Development},
  title        = {Defective oligodendrocyte development and severe hypomyelination in PDGF-A knockout mice.},
  volume       = {126},
  year         = {1999},
}