The organization and control of expression of immunoglobulin genes are being investigated. Specifically, we are studying the evolution and organization of immunoglobulin lambda genes in mice. We have cloned all of the variable (V) and constant (C) genes of this locus, which we are now trying to link up by """"""""chromosome walking."""""""" We are analyzing the specifics of lambda gene expression in SJL mice, which have a defect in lambda 1 synthesis. A nucleotide change in C lambda 1 is genetically linked with the defect. Additional DNA cloning and RNA and protein studies are aimed at determining the exact basis of the defect. Furthermore, we are studying the mechanisms of allelic exclusion and V-C gene rearrangement by gene transfection experiments. Finally, we are trying to determine the basis for the very localized somatic mutations in V genes that are expressed. (AB)

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA025754-13
Application #
3167000
Study Section
Allergy and Immunology Study Section (ALY)
Project Start
1979-03-01
Project End
1987-02-28
Budget Start
1985-03-01
Budget End
1986-02-28
Support Year
13
Fiscal Year
1985
Total Cost
Indirect Cost
Name
University of Washington
Department
Type
Schools of Medicine
DUNS #
135646524
City
Seattle
State
WA
Country
United States
Zip Code
98195
O'Brien, R L; Brinster, R L; Storb, U (1987) Somatic hypermutation of an immunoglobulin transgene in kappa transgenic mice. Nature 326:405-9
Storb, U (1987) Transgenic mice with immunoglobulin genes. Annu Rev Immunol 5:151-74
Storb, U; Ritchie, K A; O'Brien, R et al. (1986) Expression, allelic exclusion and somatic mutation of mouse immunoglobulin kappa genes. Immunol Rev 89:85-102
Storb, U; Pinkert, C; Arp, B et al. (1986) Transgenic mice with mu and kappa genes encoding antiphosphorylcholine antibodies. J Exp Med 164:627-41
Storb, U; Denis, K A; Brinster, R L et al. (1985) Pre-B cells in kappa-transgenic mice. Nature 316:356-8