Distinct hypomyelinated phenotypes in MBP-SV40 large T transgenic mice.
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.
Jensen
N A
NA
Division of Biology, California Institute of Technology, Pasadena.
Smith
G M
GM
Shine
H D
HD
Garvey
J S
JS
Hood
L
L
D000818:Animals; D000952:Antigens, Polyomavirus Transforming / Q000096:biosynthesis* / Q000276:immunology; D001259:Ataxia / Q000235:genetics / Q000503:physiopathology; D002490:Central Nervous System / Q000378:metabolism / Q000648:ultrastructure; D003001:Cloning, Molecular; D004247:DNA / Q000737:chemistry; D003711:Demyelinating Diseases / Q000235:genetics* / Q000378:metabolism; D005260:Female; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D008822:Mice, Transgenic; D008854:Microscopy, Electron; D004676:Myelin Basic Protein / Q000235:genetics / Q000378:metabolism*; D009186:Myelin Sheath / Q000502:physiology* / Q000648:ultrastructure; D009836:Oligodendroglia / Q000378:metabolism; D010525:Peripheral Nerves / Q000378:metabolism / Q000648:ultrastructure; D010641:Phenotype; D011401:Promoter Regions, Genetic / Q000235:genetics; D013116:Spinal Cord / Q000648:ultrastructure; D014202:Tremor / Q000235:genetics
D000952:Antigens, Polyomavirus Transforming; D004676:Myelin Basic Protein; D004247:DNA