The objectives of the proposed research are to identify and characterize in mice craniofacial disorders that are reliable genetic and physiological models for human craniofacial dysmorphologies and to share these models with the scientific public. The proposed research will include screening for new spontaneous and induced mutations, comprehensive genetic studies, preliminary characterization studies (clinical examination, basic histology, evaluation of bone density and skeletal anomalies, dentition, vision and hearing), and identification of the mutated gene in the best models by candidate gene testing and positional cloning. We will provide these models to the scientific community expeditiously via website notification and will distribute live mice using programs already in place at The Jackson Laboratory. This proposal has three specific aims: 1. To discover and characterize (genetically and phenotypically) new mouse craniofacial mutations to provide the scientific community with model systems for research on facial, dental, eye, ear, and skull development and mouse models of human craniofacial syndromes. 2. To identify the mutated genes in three new mutants already genetically mapped and partially characterized: Dhe, a semi-dominant mutation causing an underdeveloped lower jaw, abnormal tooth development, small ears, and a sparse, rough coat; Lse, a semi-dominant mutation causing low set ears, skull and eye abnormalities, and nee, a recessive mutation causing a blunted face, bulging eyes, and intermediate hearing loss. 3. To execute a sharing plan whereby new models will be made available rapidly to the scientific community through our established web sites and live mice will be distributed via the existing shipping program within The Jackson Laboratory. ? ?
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