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Distinct hypomyelinated phenotypes in MBP‐SV40 large T transgenic mice
Author(s) -
Jensen Niels A.,
Smith G. M.,
Shine H. D.,
Garvey J. S.,
Hood L.
Publication year - 1993
Publication title -
journal of neuroscience research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.72
H-Index - 160
eISSN - 1097-4547
pISSN - 0360-4012
DOI - 10.1002/jnr.490340302
Subject(s) - biology , myelin , oligodendrocyte , central nervous system , myelin basic protein , genetically modified mouse , antigen , transgene , phenotype , immunocytochemistry , immunohistochemistry , spinal cord , microbiology and biotechnology , immunology , neuroscience , endocrinology , genetics , gene
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 prodominantly 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. © 1993 Wiley‐Liss, Inc.