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Developmental Expression of Myelin Protein Genes in Dysmyelinating Mutant Mice: Analysis by Nuclear Run-Off Transcription Assay, In Situ Hybridization, and Immunohistochemistry

Authors


  • The present address of Dr. C. Shiota is Department of Pathology, Wakayama Medical College, 9-Bancho, Wakayama 640, Japan.

Address correspondence and reprint requests to Dr. K. Mikoshiba at Division of Regulation of Macromolecular Function, Institute for Protein Research, Osaka University, Yamadaoka 3-2, Suita. Osaka 565, Japan.

Abstract

Abstract: Gene expression for myelin proteolipid protein (PLP) and myelin basic protein (MBP) in the dysmyelinating mutant mice shiverer and jimpy was analyzed by nuclear run-off transcription assay, in situ hybridization, and immunohistochemistry. The level of PLP transcription in shiverer brains was lower than that in controls at postnatal day 18 but relatively higher at later stages. In spite of the considerable amount of hybridization with PLP cDNA, immunoreaction for PLP was greatly reduced in shiverer mice throughout their lives, probably owing to a defect in the assembly of PLP into myelin. Abnormal deposition of PLP in oligodendroglial cell bodies suggested that transport of PLP to myelin is delayed in shiverer brains. The number of oligodendrocytes expressing PLP mRNA was drastically reduced in jimpy mice. MBP mRNA in jimpy mice is localized preferentially in oligodendroglial cell bodies, a result suggesting that oligodendrocytes in jimpy are mostly the immature type. Although transcriptional activity of the MBP gene in jimpy was greatly reduced, a finding reflecting the decrease in the number of mature oligodendrocytes, that of the PLP gene remained high at early stages. The discrepancy of the two gene expressions is discussed relative to the role of PLP transcripts at early stages of myelination.

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