ICR/IAn mice present a deficiency in phosphorylase kinase activity; the extent of this deficiency is less in some tissues (Lyon, S. B. Biochem. Genet. 4, 169–185 (1970)] than in skeletal muscle, where enzyme activity is 0.3% of normal [Cohen, P. T. W. & Cohen, P. FEBS Lett. 29, 113–115 (1973)]. New‐born mice of this strain were also reported (Lyon, 1970) to reveal a small amount of skeletal muscle enzyme activity. The properties of these residual phosphorylase kinases were compared to those of control C57BL mice, with reference to control muscle and liver enzymes which were shown to be of different molecular species [Daegelen‐Proux et al. Biochim. Biophys. Acta, 452, 398–405 (1976)]. The properties investigated were the immunological reactivity against an antiserum raised against muscle phosphorylase kinase, the thermal stability and the Ca2+ dependency. The results suggest that the muscle enzyme from the new‐born ICR/IAn mice and the heart enzyme from adult deficient mice are different to the muscle enzyme from adult normal mice, but they have properties in common with normal adult liver enzyme. These results lead to the conclusion that there exists in the muscle of I strain a ‘foetal form’ of phosphorylase kinase, the activity of which decreases progressively after birth. Our work also confirmed the observations made by Cohen et al. [Eur. J. Biochem. 66, 347–356 (1976)] which showed that there is no evidence for the existence of a cross‐reacting material in the muscle of adult deficient mice.

McArdle's disease is due to the lack of activity of muscle glycogen phosphorylase. We investigated the presence of an inactive protein by two techniques: (a) Bidimensional protein maps, using a modification of the original O'Farrell technique allowing location of phosphorylase. (b) Purification of enzyme from crude muscle extracts, using an immunoaffinity microchromatographic procedure. Protein maps of three patients were obtained. No protein was detected at the normal (97 K) position of phosphorylase but 70 and 60 K spots were visible. Results of enzyme purificaton by immunoaffinity were negative for one patient, whereas a small band of phosphorylase-like material was detected in the other. Our results confirm the molecular heterogeneity of the disease. We think such methods might be useful for investigating other genetic diseases.

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