Streamline assessment of early lethal phenotypes in the mouse

University Of Massachusetts Amherst, Amherst MA

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Abstract

? DESCRIPTION (provided by applicant): Streamline assessment of early lethal phenotypes in the mouse. Although the generation of a loss of function allele at every locus in the mouse genome is well underway, there is a gap in established pipelines for assessment of early lethal phenotypes. Here we propose a simple and efficient strategy for characterization of up to 200 early lethal phenotypes occurring between fertilization and organogenesis. The proposed work capitalizes on techniques that our team performs and publishes routinely, maximizing the data generation by eliminating training and troubleshooting steps as well as boosting our individual research programs by providing novel phenotypes of interest. Our strategy relies on an initial morphological assessment of mutant phenotypes and classification into three different categories: pre- implantation, gastrulation and post-gastrulation lethals. A second round of analysis will provide a more detailed analysis of the phenotype. The characterization of early embryonic lethal alleles will be invaluable towards understanding genetic pathways of basic embryo development providing new directions for studies in stem cell biology and regenerative medicine. Our proposal dovetails perfectly with existing phenotyping efforts and fills an essential need to characterize early lethal phenotypes towards functional annotation of the genome.