The overall goal of the proposed experiments is to understand the cis-acting elements through which switch recombination is regulated. The investigator has established a transgenic mouse model that measures properly regulated germline transcription from the murine g1 gene. He has also prepared a line of transgenic mice that can undergo switch recombination to g1. He will investigate the function of the cis-acting elements in the g1 gene by further localization of the elements in transgenes, by analysis of their ability to interact with other promoters, by their deletion from the endogenous g1 gene and by studying the effect of mutations of the cis-acting elements on both germline transcription and switch recombination. He will also study the transcriptional regulation of the g2a gene, emphasizing both cis-acting elements in the g2a gene and in the heavy chain 3 regulatory region.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA039068-19
Application #
2894625
Study Section
Allergy and Immunology Study Section (ALY)
Program Officer
Mccarthy, Susan A
Project Start
1984-09-01
Project End
2002-07-31
Budget Start
1999-08-01
Budget End
2000-07-31
Support Year
19
Fiscal Year
1999
Total Cost
Indirect Cost
Name
University of Michigan Ann Arbor
Department
Microbiology/Immun/Virology
Type
Schools of Medicine
DUNS #
791277940
City
Ann Arbor
State
MI
Country
United States
Zip Code
48109
Collins, John T; Shi, Jian; Burrell, Bryna E et al. (2006) Induced expression of murine gamma2a by CD40 ligation independently of IFN-gamma. J Immunol 177:5414-9
Dunnick, Wesley A; Shi, Jian; Graves, Kevin A et al. (2005) The 3' end of the heavy chain constant region locus enhances germline transcription and switch recombination of the four gamma genes. J Exp Med 201:1459-66
Gao, Ning; Dang, Tam; Dunnick, Wesley A et al. (2005) Receptors and counterreceptors involved in NK-B cell interactions. J Immunol 174:4113-9
Berton, Michael T; Linehan, Leslie A; Wick, Kerilyn R et al. (2004) NF-kappaB elements associated with the Stat6 site in the germline gamma1 immunoglobulin promoter are not necessary for the transcriptional response to CD40 ligand. Int Immunol 16:1741-9
Dunnick, Wesley A; Shi, Jian; Graves, Kevin A et al. (2004) Germline transcription and switch recombination of a transgene containing the entire H chain constant region locus: effect of a mutation in a STAT6 binding site in the gamma 1 promoter. J Immunol 173:5531-9
Williams, Bret R; Mirzoeva, Olga K; Morgan, William F et al. (2002) A murine model of Nijmegen breakage syndrome. Curr Biol 12:648-53
Adams, K; Ackerly, H; Cunningham, K et al. (2000) A DNase I hypersensitive site near the murine gamma1 switch region contributes to insertion site independence of transgenes and modulates the amount of transcripts induced by CD40 ligation. Int Immunol 12:1705-13
Collins, J T; Dunnick, W A (1999) Cutting edge: IFN-gamma regulated germline transcripts are expressed from gamma2a transgenes independently of the heavy chain 3' enhancers. J Immunol 163:5758-62
Cunningham, K; Ackerly, H; Claflin, L et al. (1998) Germline transcription and recombination of a murine VDJmudeltagamma1 transgene. Int Immunol 10:1027-37
Cunningham, K; Ackerly, H; Alt, F et al. (1998) Potential regulatory elements for germline transcription in or near murine Sgamma1. Int Immunol 10:527-36

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