The T/t-complex has an important role in the genetic control of cellular commitment in normal early development. Several important new studies make the recessive -lethal mutations more accessible to molecular analysis: (1) two of them have been mapped within the well characterized MHC; 12 is between H-2D and TL, and w5 is genetically inseparable from H-2K. (2) 185 kb of the H-2K region of -haplotypes has been cloned in cosmids and restriction mapped. Preliminary results indicate this region contains several early embryo-expressed sequences. (3) the structural gene for a -associated cell surface antigen, gp87, has two copies physically mapped, one in the Qa region and one between the two H-2K genes. We intend to use this recent information to try to identify and structurally characterize interesting early embryo-expressed genes including w5 and 12. The overall approaches we propose are: 1) to search the H-2K region cosmids for embryo expressed genes using cDNA from embryonal carcinoma cells, and to use unique copy probes from the genomic cosmids to probe available cDNA libraries from normal early embryos. In an effort to specifically identify w5, we propose to compare its H-2K region structure to that of a revertent. 2) The second approach is to structurally study the organization of the D-TL region of -haplotypes where the 12 gene is located. We will use CHEF gel analysis and existing recombinants to refine the map position of 12. 3) Finally, we will continue the molecular analysis of the -associated glycoprotein antigen """"""""glycoproteins 87"""""""" by retrieving and sequencing clones from cDNA libraries. We will study the expression of interesting genes identified using a variety of techniques including in situ hybridization to cut sections of embryos and in the case of the mutants, transgenic embryo rescue. 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.

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National Cancer Institute (NCI)
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Mammalian Genetics Study Section (MGN)
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University of Texas Austin
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Yeom, Y I; Abe, K; Artzt, K (1992) Evolution of the mouse H-2K region: a hot spot of mutation associated with genes transcribed in embryos and/or germ cells. Genetics 130:629-38
Ebersole, T; Lai, F; Artzt, K (1992) New molecular markers for the distal end of the t-complex and their relationships to mutations affecting mouse development. Genetics 131:175-82
Ebersole, T; Rho, O; Artzt, K (1992) The proximal end of mouse chromosome 17: new molecular markers identify a deletion associated with quakingviable. Genetics 131:183-90
Yeom, Y I; Abe, K; Bennett, D et al. (1992) Testis-/embryo-expressed genes are clustered in the mouse H-2K region. Proc Natl Acad Sci U S A 89:773-7
Uehara, H; Abe, K; Flaherty, L et al. (1991) Molecular organization of the D-Qa region of t-haplotypes suggests that recombination is an important mechanism for generating genetic diversity of the major histocompatibility complex. Mamm Genome 1:92-9
Ark, B; Gummere, G; Bennett, D et al. (1991) Mapping of the Pim-1 oncogene in mouse t-haplotypes and its use to define the relative map positions of the tcl loci t0(t6) and tw12 and the marker tf (tufted). Genomics 10:385-9
Yeom, Y I; Ha, H S; Balling, R et al. (1991) Structure, expression and chromosomal location of the Oct-4 gene. Mech Dev 35:171-9
Ha, H; Abe, K; Artzt, K (1991) Primary structure of the embryo-expressed gene KE2 from the mouse H-2K region. Gene 107:345-6
Ha, H; Howard, C A; Yeom, Y I et al. (1991) Several testis-expressed genes in the mouse t-complex have expression differences between wild-type and t-mutant mice. Dev Genet 12:318-32
Howard, C A; Gummere, G R; Lyon, M F et al. (1990) Genetic and molecular analysis of the proximal region of the mouse t-complex using new molecular probes and partial t-haplotypes. Genetics 126:1103-14

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