The proposed research involves analysis of mice which have alteredexpression of cardiac myofibrillar genes via gene targeting or transgenesis.We have developed a line of mice bearing a targeted disruption/deletion of the alpha myosin heavy chain locus (alpha-MyHC). Mice homozygous for this mutation die in utero between day 11 and 12.5 post coitum (p.c.). Preliminary data indicate that these, as well as embryos bearing the mutation in the heterozygous state, have ventricular wall and outflow tract defects. To analyze this phenotype rigorously by conventional methods would require thick sectioning and scanning electron microscopic examination. Since thick sectioning destroys the tissue and yields information from only a single plane, many animals would have to be examined. This is impractical due to the expense and effort required to produce and identify homozygous mutant embryos. This would be exacerbated if the phenotype is found to be variably penetrant (as is the adult phenotype). Subjecting a relatively small number of homozygous mutant embryos to analysis by MR microscopy would allow examination of each embryonic heart in any plane and at any level of the organ. Changes in the outflow tract and associated vessels would be apparent since they would not be affected by dissection and even more importantly, tissue would be available for subsequent analyses in order to correlate structural and biochemical deficits. We estimate that examination of 3-5 embryos of each genotype (wild type, homozygous mutant and heterozygous mutant) would be sufficient.
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