Single base substitution in codon 74 of the MD rat myelin proteolipid protein gene.

- Simons R, Riordan JR

Ann N Y Acad Sci 1990;605:146-54.

The myelin-deficient (md) rat is one of several X-linked animal mutants that have severe dysmyelination in the central nervous system. It appears in all to be the result of mutations in the myelin proteolipid protein gene which is located on the long arm of the X-chromosome. To identify the md rat mutation, we isolated and sequenced cDNAs corresponding to PLP and DM-20 mRNAs from the brain of hemizygous affected males. The only consistent sequence difference between these and normal rat sequences was the substitution of a C for an A at the first position of codon 74, resulting in a threonine to proline amino acid change. The presence of this helix-breaking amino acid in the second hydrophobic alpha-helical segment of the protein might be expected to influence its ability to interact with the membrane. PCR amplification and sequencing of the corresponding genomic regions were used to confirm the presence of the single base change in the hemizygote and both normal and mutant versions in the heterozygotes. It is interesting that this change, like those detected in other X-linked myelin disorders, involves an amino acid replacement within a hydrophobic alpha-helical segment of the PLP protein. Disruption of these structures apparently has severe consequences for the ability of PLP to contribute normally to myelination.

This abstract at PubMed.