The initiation of X inactivation during early embryogenesis and the subsequent maintenance of the inactive X condition throughout development are central issues in the X-inactivation process. These features and the succeeding reactivation during oogenesis are unique developmental changes which produce the coordinate regulation of an entire X chromosome. This proposal is a broadly based approach to studying the X-inactivation process in the mouse. Our experimental strategies draw upon using X-chromosome gene variation we have recovered from a wide sampling of the mouse gene pool to follow the expression of specific X chromosomes. We have extended this strategy to identifying DNA variation which can be used to follow DNA methylation on active and inactive X-chromosome genes. We are now in a position to extend our use of naturally occurring variation of X chromosome genes to efficiently screen mutagen treated stocks for additional X chromosome markers and to identify mutations which provide an opportunity to pursue a genetic analysis of X-chromosome regulation during the inactivation process. We are also extending the use of biochemical markers of X-chromosome genes to examine the expression of X-chromosome genes in X;autosome translocations. The expression of genes which are either proximal or distal to the translocation will provide some insight into the site(s) which establish X-chromosome identity in the inactivation process. This proposal also describes experiments to study X-chromosome reactivation in embryonal carcinoma cell-somatic cell hybrids. This work will provide important information about the inactivation and reactivation process and it offers an opportunity to develop new experimental approaches to studying X-chromosome regulation.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM024125-12
Application #
3272072
Study Section
(SSS)
Project Start
1977-08-01
Project End
1990-08-31
Budget Start
1988-09-01
Budget End
1989-08-31
Support Year
12
Fiscal Year
1988
Total Cost
Indirect Cost
Name
Roswell Park Cancer Institute Corp
Department
Type
DUNS #
City
Buffalo
State
NY
Country
United States
Zip Code
14263
Chapman, V M; Keitz, B T; Disteche, C M et al. (1991) Linkage of amelogenin (Amel) to the distal portion of the mouse X chromosome. Genomics 10:23-8
Grant, S G; Chapman, V M (1991) Detailed genetic mapping of the A-raf proto-oncogene on the mouse X chromosome. Oncogene 6:397-402
Matsuda, Y; Chapman, V M (1991) In situ analysis of centromeric satellite DNA segregating in Mus species crosses. Mamm Genome 1:71-7
Chapman, V M; Stephenson, D A; Mullins, L J et al. (1991) Linkage of the erythroid transcription factor gene (Gf-1) to the proximal region of the X chromosome of mice. Genomics 9:309-13
Singer-Sam, J; Grant, M; LeBon, J M et al. (1990) Use of a HpaII-polymerase chain reaction assay to study DNA methylation in the Pgk-1 CpG island of mouse embryos at the time of X-chromosome inactivation. Mol Cell Biol 10:4987-9
Chapman, V M; Keitz, B T; Stephenson, D A et al. (1990) Linkage of a gene for neural cell adhesion molecule, L1 (CamL1) to the Rsvp region of the mouse X chromosome. Genomics 8:113-8
Mullins, L J; Stephenson, D A; Grant, S G et al. (1990) Efficient linkage of 10 loci in the proximal region of the mouse X chromosome. Genomics 7:19-30
Sigmund, C D; Okuyama, K; Ingelfinger, J et al. (1990) Isolation and characterization of renin-expressing cell lines from transgenic mice containing a renin-promoter viral oncogene fusion construct. J Biol Chem 265:19916-22
Disteche, C M; McConnell, G K; Grant, S G et al. (1989) Comparison of the physical and recombination maps of the mouse X chromosome. Genomics 5:177-84
Grant, S G; Swiatek, D A; Benz, R A et al. (1988) Golden: a novel coat color mutant in the wild mouse Mus caroli. J Hered 79:151-4

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