9306850 Sutko This proposal will attempt to determine the molecular and cellular changes that occur in the crooked neck dwarf (cn) mutation in chickens. This mutation causes changes in embryonic skeletal muscle that are lethal to the embryo. These changes include muscle dysfunction and the inability to maintain embryonic skeletal muscles and connective tissues which result in skeletal muscle degeneration and cell death. This investigator has found that cn skeletal muscle cells maintained in primary cultures form myotubes which degenerate and die, which is similar to what occurs in ovo. This project will identify the cellular components and processes in how these changes cause the lethal effects in the mutant. An in vitro system with the properties of the mutant phenotypes will permit application of a number of cell and molecular biological techniques. The hypothesis of these studies is that a failure to make normal alpha ryanodine receptor, a skeletal muscle sarcoplasmic reticulum calcium release channel, is the initial defect of the cn mutation. A knowledge of the proteins and processes that are altered to produce the cn phenotype will provide insights into the development of embryonic muscle and factors involved in muscle cell viability. ***
