Transcriptional regulation studies of myelin-associated genes in myelin-deficient mutant rats.
To identify and assess the consequences of the mutation in myelin-deficient (md) rats, the myelin proteolipid protein (PLP) gene and its expression were studied in md rats. Southern blots of the PLP gene demonstrated that no major deletions or insertions have occurred in this gene. In addition, the mutation in this gene does not result in a splicing defect in the RNAs, since all exons are represented in md PLP RNAs. These data are consistent with results in another laboratory indicating that a point mutation in the PLP gene in md rats results in a single amino acid alteration in the protein. To elucidate the molecular mechanisms producing reduced levels of PLP, myelin basic protein (MBP) and glycerol phosphate dehydrogenase (GPDH) mRNAs, and their corresponding proteins in md rats, in vitro transcription assays were performed. Transcription of the PLP gene in nuclei isolated from 23-day-old md rat brains was dramatically reduced relative to normal tissue. Thus, the single amino acid alteration in this protein alters the regulation of transcription of this gene. In contrast, the transcriptional activities of the MBP and GPDH genes in md rats were indistinguishable from normal animals. Thus, the lower level of MBP and GPDH mRNA and protein in md rats relative to normal results from a posttranscriptional event.
Kumar
S
S
Department of Psychiatry, UCLA School of Medicine.
Macklin
W B
WB
Gordon
M N
MN
Espinosa de los Monteros
A
A
Cole
R
R
Scully
S A
SA
de Vellis
J
J
D000818:Animals; D015139:Blotting, Southern; D002467:Cell Nucleus / Q000378:metabolism; D003711:Demyelinating Diseases / Q000235:genetics* / Q000378:metabolism; D005091:Exons; D005993:Glycerolphosphate Dehydrogenase / Q000096:biosynthesis / Q000235:genetics; D008297:Male; D051379:Mice; D008818:Mice, Neurologic Mutants; D004676:Myelin Basic Protein / Q000096:biosynthesis / Q000235:genetics; D009185:Myelin Proteins / Q000096:biosynthesis / Q000235:genetics*; D018991:Myelin Proteolipid Protein; D009186:Myelin Sheath / Q000502:physiology*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D015719:Single-Strand Specific DNA and RNA Endonucleases; D014158:Transcription, Genetic
D004676:Myelin Basic Protein; D009185:Myelin Proteins; D018991:Myelin Proteolipid Protein; D012333:RNA, Messenger; D005993:Glycerolphosphate Dehydrogenase; D015719:Single-Strand Specific DNA and RNA Endonucleases