Mouse embryos that lack either a maternal (androgenones) or paternal (gynogenones) genetic contribution fail to develop due to functional differences between the two genomes established through genetic imprinting during gametogenesis. It has been suggested that the genetic imprints are translated into differences in gene expression through modification of imprinted genes by factors in the egg. These """"""""modifier"""""""" factors are proposed to influence the methylation status or chromatin structure of imprinted genes. The nature and function of such modifiers have yet to be determined. Recent experiments indicate that androgenetic embryos offer a useful system for studying modifiers. The developmental capacity of androgenones varies with the maternal genotype (i.e. egg composition) due to strain-dependent modification of the male pronuclei. This modification is most likely mediated by one or more strain-specific modifiers which influence the expression of genes that are required for blastocoel formation. In this proposal,l will determine whether a single or multiple modifiers is/are responsible for this modification and, if a single modifier, determine its chromosomal location by recombinant inbred mapping. Immunofluorescence microscopy will be used to test the hypothesis that developmental failure in androgenones results from a defect in the establishment or differentiation of the putative trophectoderm lineage. These experiments will provide critical background information to be used in the future to pursue the identification and characterization of the genes encoding these modifiers and the genes that are regulated by them. This will further our understanding of imprinting, which contributes to specific disorders in man.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
3R01GM049489-03S1
Application #
846980
Study Section
Mammalian Genetics Study Section (MGN)
Project Start
1992-08-01
Project End
1995-07-31
Budget Start
1994-08-01
Budget End
1995-07-31
Support Year
3
Fiscal Year
1995
Total Cost
Indirect Cost
Name
Temple University
Department
Miscellaneous
Type
Schools of Medicine
DUNS #
City
Philadelphia
State
PA
Country
United States
Zip Code
19122
Rossant, J; Guillemot, F; Tanaka, M et al. (1998) Mash2 is expressed in oogenesis and preimplantation development but is not required for blastocyst formation. Mech Dev 73:183-91
Domashenko, A D; Latham, K E; Hatton, K S (1997) Expression of myc-family, myc-interacting, and myc-target genes during preimplantation mouse development. Mol Reprod Dev 47:57-65
Latham, K E; Cosenza, S; Reichenbach, N L et al. (1996) Inhibition of growth of estrogen receptor positive and estrogen receptor negative breast cancer cells in culture by AA-etherA, a stable 2-5A derivative. Oncogene 12:827-37
Latham, K E; Litvin, J; Orth, J M et al. (1996) Temporal patterns of A-myb and B-myb gene expression during testis development. Oncogene 13:1161-8
Latham, K E (1996) X chromosome imprinting and inactivation in the early mammalian embryo. Trends Genet 12:134-8
Rambhatla, L; Latham, K E (1995) Strain-specific progression of alpha-amanitin-treated mouse embryos beyond the two-cell stage. Mol Reprod Dev 41:16-9
Latham, K E; Rambhatla, L (1995) Expression of X-linked genes in androgenetic, gynogenetic, and normal mouse preimplantation embryos. Dev Genet 17:212-22
Mann, M; Latham, K E; Varmuza, S (1995) Identification of genes showing altered expression in preimplantation and early postimplantation parthenogenetic embryos. Dev Genet 17:223-32
Latham, K E; McGrath, J; Solter, D (1995) Mechanistic and developmental aspects of genetic imprinting in mammals. Int Rev Cytol 160:53-98
Rambhatla, L; Patel, B; Dhanasekaran, N et al. (1995) Analysis of G protein alpha subunit mRNA abundance in preimplantation mouse embryos using a rapid, quantitative RT-PCR approach. Mol Reprod Dev 41:314-24

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