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The distributions of acetylcholinesterase and its molecular forms within muscles of normal and dystrophic 129/ReJ mice were established by a concomitant cytochemical and biochemical study performed on 1-mm serial sections of three predominantly fast muscles, i.e., anterior tibialis, extensor digitorum longus, and sternomastoid, as well as the slow-twitch soleus. This comparative study showed the following main findings. 1) In every muscle of both normal and dystrophic mice a) the three asymmetric forms were confined to the motor zone where they systematically codistributed with the endplates, and b) all globular forms, including G4, were concentrated at the motor zone from which they extended over the entire muscle length along a concentration gradient. 2) In the normal muscles, the perijunctional sarcoplasmic cytochemical reaction exhibited by individual fibers was grouped into a well-defined cojunctional acetylcholinesterase compartment in which the endplates were embedded. The overall intensity of the cojunctional cytochemical reaction was either high or low according to whether the muscle was predominantly fast or slow. 3) This cojunctional acetylcholinesterase compartment varied in close parallelism with G4 and thus appeared as the cytochemical correlate of the G4 molecules concentrated around the endplates. In particular, as the shape of the motor zone progressively increased in complexity along with the intricacy of the muscle fiber organization, from sternomastoid to extensor digitorum longus to anterior tibialis, so did both the relative volume occupied by the cojunctional acetylcholinesterase compartment and the proportion of G4. 4) The motor zone of the normal fast-twitch muscles characteristically differed from that of the soleus by the presence of a G4-rich environment around the endplates, which was cooperatively provided by the surrounding fibers. 5) In dystrophic muscles, this cojunctional G4-rich compartment was lost: the cojunctional cytochemical compartment was no longer discernable, while G4 was reduced to a minimal low level similar to that characteristic of the normal soleus.

Acetylcholinesterase activities and molecular forms were studied in normal and dystrophic 129/ReJ mice, focusing on four predominantly fast-twitch muscles and the slow-twitch soleus. The asymmetric and globular forms were analyzed separately so that the effect of dystrophy on each form could be determined. This comparative study showed the following. (1) In the normal condition, each muscle exhibited a distinct distribution of the molecular forms. (2) The diversity among the fast muscles resulted mainly from variations in the proportions of the three globular forms; in contrast, these muscles showed a constant and precise A12/A8/A4 ratio. (3) The slow-twitch soleus clearly differed from the other muscles in its low acetylcholinesterase activity and distinct distribution of the molecular forms, characterized by a low level of G4 and a peculiar ratio among its asymmetric forms, resulting from a relative increase of the A8 and A4 forms. (4) In dystrophic mice, the diversity of the acetylcholinesterase distribution was lost; all the fast muscles displayed profiles exhibiting the characteristics typical of the soleus. The fast-twitch extensor digitorum longus, sternomastoid, and plantaris converged towards an identical set of acetylcholinesterase molecules. (5) In contrast, the acetylcholinesterase activity and molecular forms of the soleus were only slightly affected by the disease. These results reveal that the dystrophy modifies both categories of molecular forms of acetylcholinesterase in a very precise manner. Such complex changes, which are highly reproducible in a variety of different muscles, are unlikely to result from nonspecific reactions secondary to the disease.

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