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© The Rockefeller University Press, 0021-9525/1997//871 $5.00
The Journal of Cell Biology, Volume 136, Number 4, , 1997 871-882

Subtle Neuromuscular Defects in Utrophin-deficient Mice

R. Mark Grady^*, John P. Merlie, and Joshua R. Sanes

^* Departments of Pediatrics, Molecular Biology and Pharmacology, and Anatomy and Neurobiology, Washington University School of Medicine, St. Louis, Missouri

Utrophin is a large cytoskeletal protein that is homologous to dystrophin, the protein mutated in Duchenne and Becker muscular dystrophy. In skeletal muscle, dystrophin is broadly distributed along the sarcolemma whereas utrophin is concentrated at the neuromuscular junction. This differential localization, along with studies on cultured cells, led to the suggestion that utrophin is required for synaptic differentiation. In addition, utrophin is present in numerous nonmuscle cells, suggesting that it may have a more generalized role in the maintenance of cellular integrity. To test these hypotheses we generated and characterized utrophin-deficient mutant mice. These mutant mice were normal in appearance and behavior and showed no obvious defects in muscle or nonmuscle tissue. Detailed analysis, however, revealed that the density of acetylcholine receptors and the number of junctional folds were reduced at the neuromuscular junctions in utrophin-deficient skeletal muscle. Despite these subtle derangements, the overall structure of the mutant synapse was qualitatively normal, and the specialized characteristics of the dystrophin-associated protein complex were preserved at the mutant neuromuscular junction. These results point to a predominant role for other molecules in the differentiation and maintenance of the postsynaptic membrane.

Abbreviations used in this paper: AChR, acetylcholine receptors; DPC, dystrophin-associated protein complex; ES, embryonic stem; NMJ, neuromuscular junction; RT-PCR, reverse transcription-polymerase chain reaction.

J.P. Merlie died on 27 May 1995.

 Please address all correspondence to J.R. Sanes, Department of Anatomy and Neurobiology, Washington University School of Medicine, 660 South Euclid Avenue, Box 8108, St. Louis, MO 63110. Fax: (314) 7471150.

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