I/Lyn mouse phosphorylase kinase deficiency: mutation disrupts expression of the alpha/alpha'-subunit mRNAs.
A cDNA encoding the alpha subunit of mouse skeletal muscle phosphorylase kinase was used to compare the expression of alpha mRNAs in normal and phosphorylase kinase-deficient tissues of the I/Lyn mouse. The results demonstrate that two different molecular weight species of poly(A)+ RNA in normal mouse heart and skeletal muscle hybridize to the alpha cDNA. These two mRNAs direct the synthesis of alpha protein and its isoform alpha' in a cell-free translation system. Thus, alpha and alpha' are encoded by two distinct mRNAs. The abundance of both of these mRNAs is reduced dramatically in the phosphorylase kinase-deficient skeletal muscle and heart tissues from the I/Lyn mouse strain. This result indicates that a mechanism common to both alpha and alpha' expression is disrupted by the I/Lyn mutation. The I/Lyn deficiency is inherited as an X chromosome trait. By Southern mapping of Chinese hamster-mouse cell hybrids the alpha gene was localized to the mouse X chromosome, supporting the possibility that the I/Lyn mutation is in the alpha gene. These results are discussed in terms of a cis or trans mutation influencing the expression of either a single alpha/alpha' gene or two genes encoding alpha and alpha'.
Bender
P K
PK
Department of Biology, University of Virginia, Charlottesville 22901.
Lalley
P A
PA
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002874:Chromosome Mapping; D004247:DNA / Q000235:genetics; D015870:Gene Expression; D005796:Genes; D046911:Macromolecular Substances; D051379:Mice; D008807:Mice, Inbred BALB C; D008817:Mice, Mutant Strains; D008969:Molecular Sequence Data; D009132:Muscles / Q000201:enzymology; D009154:Mutation; D009693:Nucleic Acid Hybridization; D010764:Phosphorylase Kinase / Q000172:deficiency / Q000235:genetics*; D014176:Protein Biosynthesis; D012333:RNA, Messenger / Q000235:genetics*; D012016:Reference Values; D014158:Transcription, Genetic
D046911:Macromolecular Substances; D012333:RNA, Messenger; D004247:DNA; D010764:Phosphorylase Kinase