The genes which are actually participating in four stages of early mouse embryogenesis have been constructed separately as embryo cDNA libraries in our laboratory; stage 10 (5.5 days in gestation), stage 15 (8.5 days in gestation). stage 22 (10.5 days in gestation) and stage 30 (13.5 days in gestation). From these cDNA libraries of early mouse embryos, we wish to clone the gene families which are linked to the major histo- compatibility complex (MHC) region and regulates the development of early mouse embryos. Both in man and in animals, about 15 to 60% of fertilized ova become abnormal in early pregnancy and either are spontaneously aborted or resorbed (Beer, 1986). In mice, a part of these abnormalities are attributed to genetic causes. The genes which regulate embryonic development of early mouse embryos are clustered in the proximal region of chromosome 17 which includes the MHC region (Bennett, 1975; Klein, 1975. This segment of chromosome 17 has been called the t-complex region (Silver, 1985). More than 100 mutants collected have been classified into 16 complementation groups. Each mutant blocks the embryonic development at specific butt different stages. Seven out of 16 classified groups have been studied. The locus of these 7 mutants are linked to the MHC (Artzt, 1984). The genes of tLub-1 and tW18 are located near the H-2D region and t12 is intermingled with the Qa region (Shin et al., 1984). Particularly, tW5 is linked to the H-2K1 gene of MHC within theoretical distance of 0.07 cM or 140 kilobases of DNA. Homozygous tW5/tW5 mice die around 5.5 days in gestation with disorganized embryonic tissues. using DNA probes which are specific for the t-complex region, H-2K region and class I genes of MHC, we have cloned gene families which are active only in early embryos (5.5 days and 8.5 days) but not at later stages (10.5 days and 13.5 days). Each gene family has stage and tissue specificity. The Class I genes in the Qa-Tia region (differentation genes) are active at 5.5 and 8.5 days in gestation which may function as an alternative of transplantation antigen genes (H-2K, H-2D and H-2L of later stages. The activity of Class I genes in the Qa-Tia region at early embryonic stages could explain the fact that fetuses as allografts are not rejected by the mother. The genes regulating mouse embryogenesis are spread beyond the region of MHC. We plan to clone genes in the t-complex region which are stage specific and tissue specific and study its gene organization and classify into its stages of activity.

National Institute of Health (NIH)
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
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Human Embryology and Development Subcommittee 1 (HED)
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Johns Hopkins University
Schools of Public Health
United States
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