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)

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA021651-09
Application #
3165597
Study Section
Mammalian Genetics Study Section (MGN)
Project Start
1977-09-01
Project End
1988-02-28
Budget Start
1985-03-01
Budget End
1986-02-28
Support Year
9
Fiscal Year
1985
Total Cost
Indirect Cost
Name
Sloan-Kettering Institute for Cancer Research
Department
Type
DUNS #
064931884
City
New York
State
NY
Country
United States
Zip Code
10065
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
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
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
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

Showing the most recent 10 out of 21 publications