Disorganization (Ds) is a mouse mutation with unique effects on cell lineage determination during postimplantation development in the mouse. Ds is like many homeotic mutations in Drosophila in that extra body parts are produced; it is unlike these homeotic mutations in that the nature and location of the extra part are unpredictable. Examples of congenital defects include extra limbs on the head and extra genitalia on the thorax and lower limbs. Ds is therefore a valuable model for studying the genetic aberrations of cell lineage determination leading to congenital malformations. Two studies are proposed to study the manner in which Ds directs mammalian cell lineage determination. The first concerns the origin of extra parts and has three components: a. analysis of the clonal origin of extra parts by examining expression of X- linked markers in extra parts occurring in females heterozygous for X-linked genes, b. cell autonomy of the Ds mutation by testing whether extra parts occur in aggregation chimeras of normal (+/+) and (Ds/Ds) embryos, and c. tests of whether extra parts occurring in aggregation chimeras are composed of Ds cells only, or of both. The second study concerns characterization of the Ds locus and involves preparation of a saturated genetic map of the Ds locus and tests to determine whether the Os mutation is a dominant, gain-of- function mutation by determining whether extra parts occur in experimental +/+/Ds trisomic mice. Together these studies should provide considerable insight into the manner in which the Ds mutation directs cell lineage determination during murine embryogenesis and should characterize the genetics of the Ds locus to facilitate its use in studying lineage determination.
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