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Inefficient Transcription of the Myelin Basic Protein Gene Possibly Causes Hypomyelination in Myelin‐Deficient Mutant Mice
Author(s) -
Okano Hideyuki,
Miura Masayuki,
Moriguchi Akira,
Ikenaka Kazuhiro,
Tsukada Yasuzo,
Mikoshiba Katsuhiko
Publication year - 1987
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.1987.tb04116.x
Subject(s) - myelin , mutant , myelin basic protein , transcription (linguistics) , microbiology and biotechnology , gene , biology , chemistry , genetics , neuroscience , central nervous system , philosophy , linguistics
Abstract: A hereditary dysmyelination mutation, named myelin deficient (mld ), is considered to be allelic to shiverer , a deletion mutation of the myelin basic protein (MBP) gene. The present study showed that MBP expression is greatly reduced in mld , but that it is still detectable. Northern blot analysis revealed that the pronounced decrease in the MBP level in mld resulted from a reduced mRNA level and was not caused by deletion of a large portion of the MBP gene as in shiverer . Southern blot studies with Bam HI‐digested chromosomal DNA suggested some part of the MBP gene, at least the 5′‐portion, was duplicated in mld . These results indicated that the mld and shiverer mutations were different from each other, even though genetic allelism between the two was reconfirmed. We also examined the developmental pattern of the gene expression of MBP and that of another protein, myelin proteolipid protein (PLP), specifically expressed in the oligodendrocyte, in mld by RNA dot blot study. The mRNA level of MBP in mld was greatly reduced during the active myelination stages, gradually increasing and remaining constant in the later stages. The PLP‐mRNA content in mld was almost normal (60–80% that of control) at any stage of development. All these findings imply that the primary defect in mld is due to reduced transcriptional activity of the MBP gene.