Structure and Expression of Myelin Basic Protein Gene Sequences in the mld Mutant Mouse: Reiteration and Rearrangement of the MBP Gene

• Published in: Genetics (Austin) Vol. 116; no. 3; pp. 447 - 464
• Main Authors: Akowitz, Alfred A, Barbarese, Elisa, Scheld, Kathy, Carson, John H
• Format: Journal Article
• Language: English
• Published: Bethesda, MD Genetics Soc America 01.07.1987; Genetics Society of America
• Subjects: Animals; Biological and medical sciences; Chromosome Mapping; Demyelinating Diseases - genetics; DNA Restriction Enzymes; Fundamental and applied biological sciences. Psychology; Gene Expression Regulation; Genes; Genes. Genome; Investigations; Mice; Mice, Neurologic Mutants - genetics; Molecular and cellular biology; Molecular genetics; Mutation; Myelin Basic Protein - genetics; Phenotype; Vertebrata; Mammalia; Mouse; Myelin; Gene product; Basic protein; Rodentia; Restriction map; Gene organization; Gene expression; Neurological mutation
• ISSN: 0016-6731; 1943-2631; 1943-2631
• DOI: 10.1093/genetics/116.3.447

The mld mutation on chromosome 18 in the mouse is a putative allele of the shiverer (shi) mutation. We have analyzed the structure of myelin basic protein (MBP) gene sequences in mld DNA by restriction mapping of genomic DNA. The results indicate that the mld chromosome carries two copies of the MBP structural gene, one of which is intact and one of which is interrupted. Genetic analysis indicates that the interrupted gene is close to the intact MBP structural gene and cosegregates with the mld mutation. We have also analyzed the levels of MBP polypeptides and MBP-specific mRNA in wild-type, homozygous and heterozygous shiverer and mld mice and in mice carrying both mutations. The results indicate that both shi and mld are cis-acting codominant mutations that cause severely reduced steady state levels of MBP-specific mRNA and MBP polypeptides in the brain. We have analyzed the total number of oligodendrocytes and the number of MBP-positive oligodendrocytes in mld and shi brain primary cultures. In shi cultures, none of the oligodendrocytes expresses MBP. However, in mld cultures, approximately 5% of the oligodendrocytes express MBP. The nature of the "revertant" mld oligodendrocytes is not known.