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The molecular basis of phosphorylase kinase deficiency was investigated in ICR/IAn mice, which show less than 0.2% of normal activity in skeletal muscle (Cohen, P.T.W. and Cohen, P., 1973). The genetics of the deficiency indicate it is a single gene defect on the X-chromosome (Lyon, J.B., 1970). Phosphorylase kinase was purified from skeletal muscle of a control strain, C3H/He-mg, by three different procedures. (a) Ammonium sulphate precipitation and gel filtration on Sepharose 4B. (b) Hydrophobic chromatography and affinity chromatography on Sepharose 4B to which antibody to rabbit muscle phosphorylase kinase has been linked covalently. (c) Precipitation from muscle extracts with anti-phosphorylase kinase antibody. All three procedures showed C3H/He-mg phosphorylase kinases were similar to the rabbit muscle enzymes, the structures of the two isoenzymes being (alphabetagamma)4 and (alpha'betagamma)4 respectively. The proportion of the (alpha'betagamma)4 isoenzyme relative to the (alphabetagamma)4 isoenzyme was however about 1:1 in murine muscle compared to about 1:10 in rabbit muscle. Since the alpha and alpha' subunits appear to be distinct gene products, the defect in ICR/IAn mice cannot be caused by a mutation in the genes coding for either the alpha or alpha'chains, or 50% of normal activity would be observed. All three procedures for C3H/He-mg mice failed to detect any of the four subunits alpha, alpha', beta and gamma in ICR/IAn mice, suggesting that all four chains are absent in the deficiency. An allele for the beta-subunit was identified in rabbits, and the inheritance of the allele showed that it was determined by an autosomal gene. Assuming conservation of X-linkage between mammals, the defect in ICR/IAn mice cannot be caused by a mutation in a beta-subunit gene. It is proposed that ICR/IAn mice are defective in a control gene located on the X-chromosome which is required for the expression of structural genes, at least one of which, the gene for the beta-subunit, is located on an autosome. The results imply that interchromosomal transfer of information takes place during the synthesis of phosphorylase kinase.
P T Cohen, and
A Burchell, and
P Cohen
April 1973,
European journal of biochemistry,
P T Cohen, and
A Burchell, and
P Cohen
July 1992,
Proceedings of the National Academy of Sciences of the United States of America,
P T Cohen, and
A Burchell, and
P Cohen
January 1983,
Methods in enzymology,
P T Cohen, and
A Burchell, and
P Cohen
April 2000,
Neuropediatrics,
P T Cohen, and
A Burchell, and
P Cohen
April 1986,
Neurology,
P T Cohen, and
A Burchell, and
P Cohen
February 2010,
Neuromuscular disorders : NMD,
P T Cohen, and
A Burchell, and
P Cohen
September 1973,
Biochemical and biophysical research communications,
P T Cohen, and
A Burchell, and
P Cohen
April 1971,
The Journal of biological chemistry,
P T Cohen, and
A Burchell, and
P Cohen
February 1973,
Biochemistry,
P T Cohen, and
A Burchell, and
P Cohen
December 1980,
The Biochemical journal,
