Distinct hypomyelinated phenotypes in MBP-SV40 large T transgenic mice

J Neurosci Res. 1993 Feb 15;34(3):257-64. doi: 10.1002/jnr.490340302.

Abstract

To study the effect of SV40 large T-antigen expression in myelin-forming cells of both the central and peripheral nervous system, a series of transgenic mice were generated expressing the SV40 large T-antigen under control of the myelin basic protein (MBP) promoter. Two neurologic phenotypes, designated A and B, appeared among individual transgenic founders and their progeny. The A mice developed a severe action tremor at about 10 days of age that progressed into periods of convulsions and early death by three to four weeks of age. In contrast, the B mice exhibited a progressive hindlimb ataxia and had a more normal lifespan. The A mice displayed hypomyelinating lesions in the central nervous system (CNS), whereas the B mice had lesions in either the peripheral nervous system (PNS) alone or in both the PNS and CNS. Immunohistochemical staining of spinal cord sections of a type A mouse showed a substantial depletion in MBP. Moreover, T-antigen-positive cells appeared predominantly in white matter tracts as randomly distributed single cells. Double labeling immunocytochemistry demonstrated that some of these T-antigen-positive cells were positive for oligodendrocyte differentiation markers MBP and O4. Thus, T-antigen expression appeared to coincide with a terminal stage of oligodendrocyte differentiation.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Antigens, Polyomavirus Transforming / biosynthesis*
  • Antigens, Polyomavirus Transforming / immunology
  • Ataxia / genetics
  • Ataxia / physiopathology
  • Central Nervous System / metabolism
  • Central Nervous System / ultrastructure
  • Cloning, Molecular
  • DNA / chemistry
  • Demyelinating Diseases / genetics*
  • Demyelinating Diseases / metabolism
  • Female
  • Immunohistochemistry
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Inbred DBA
  • Mice, Transgenic
  • Microscopy, Electron
  • Myelin Basic Protein / genetics
  • Myelin Basic Protein / metabolism*
  • Myelin Sheath / physiology*
  • Myelin Sheath / ultrastructure
  • Oligodendroglia / metabolism
  • Peripheral Nerves / metabolism
  • Peripheral Nerves / ultrastructure
  • Phenotype
  • Promoter Regions, Genetic / genetics
  • Spinal Cord / ultrastructure
  • Tremor / genetics

Substances

  • Antigens, Polyomavirus Transforming
  • Myelin Basic Protein
  • DNA