The T/t complex has a role in the specification of sets of cell surface antigens that appear to be important in controlling cell interactions and recognition during early development. Two important new studies increase the power of the T/t complex as a model of this control: (1) the antigen(s) associated with one of the lethal mutations (t?w18?) has been localized in time and place to the site of genetically caused dysfunction in the mutant embryo; and (2) several different t-lethal genes have been mapped; they are nonallelic and represent an apparent gene family spread over 20 cM of chromosome 17 with H-2 situated anomalously in the middle of them. We intend to study genetically relevant genes in t-mutant chromatin by taking advantage of our new-found ability to map them: (1) by classical breeding experiments; and (2) by recombinant DNA technology. Our long-term objective is to understand the molecular mechanisms and genetic control of cellular commitment in normal early development and noncommitment in embryonal tumors. The lethal genes of the T/t-complex reveal the existence of a series of wild-type genes that have an important role in the control of early embryonic development. We have used a combination of classical Mendelian genetics and molecular genetics to provide a detailed map of the t-region of mouse chromosome 17. Three important findings have emerged: (1) the entire major histocompatibility complex [MHC] is inverted in t-haplotypes; (2) the t-lethals are arranged in three clusters, the largest of which surrounds and is intermingled with the MHC; and (3) different t genes, separated by as much as 15 cM, can act as a functional unit in cis/trans tests implying that genetic plasticity may play a role in mammalian development. (CS)
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