Our laboratory studies the mechanisms that regulate the expression and recombination of one of the Ig gene clusters, IgH. By analyzing naturally occurring as well as artificially generated (transgenic and knock-out) mutant mouse strains, we are characterizing the DNA regulatory elements responsible for the coordinated rearrangements of the IgH gene, and the protein factors directly involved in the recombination process. Using molecular techniques, we have already identified local regulatory elements that control CSR to individual genes, as well as DNA sequences whose activity spans the entire IgH cluster. A second goal of our studies is to study the mechanism of action of certain Zn-chelating compounds, which we have recently shown to be able to inhibit CSR. Finally, we are conducting genetic studies aimed at identifying the mouse gene responsible for a new type of immunodeficiency that leads to defective antibody responses to polysaccharide antigens.

Smith HC, Bottaro A, Sowden MP, Wedekind JE. Activation induced deaminase: the importance of being specific. Trends Genet. 20:224-7, 2004.

Young FM, Pinkert CA, Bottaro A. Analysis of Lymphocyte Development and Function Using the RAG-Deficient Blastocyst Complementation System. Methods Mol Biol. 271:77-90, 2004.

Anolik J, Looney RJ, Bottaro A, Sanz I, Young F. Down-regulation of CD20 on B cells upon CD40 activation. Eur J Immunol. 33:2398-409, 2003.

Lee SC, Bottaro A, Insel RA. Activation of terminal B cell differentiation by inhibition of histone deacetylation. Mol Immunol. 39:923-32, 2003.

Kuzin II, Snyder JE, Ugine GD, Wu D, Lee S, Bushnell T Jr, Insel RA, Young FM, Bottaro A. Tetracyclines inhibit activated B cell function. Int Immunol. 13:921-31, 2001.

Borghesani PR, Alt FW, Bottaro A, Davidson L, Aksoy S, Rathbun GA, Roberts TM, Swat W, Segal RA, Gu Y. Abnormal development of Purkinje cells and lymphocytes in Atm mutant mice. Proc Natl Acad Sci U S A. 97:3336-41, 2000.

Kuzin II, Ugine GD, Wu D, Young F, Chen J, Bottaro A. Normal isotype switching in B cells lacking the I mu exon splice donor site: evidence for multiple mu-like germline transcripts. J Immunol. 164:1451-7, 2000.

Brusco A, Saviozzi S, Cinque F, Bottaro A, DeMarchi M. A recurrent breakpoint in the most common deletion of the Ig heavy chain locus (del A1-GP-G2-G4-E). J Immunol 163:4392-8, 1999.

Sakai E, Bottaro A, Alt FW. The Ig heavy chain intronic enhancer core region is necessary and sufficient to promote efficient class switch recombination. Int Immunol 11:1709-13, 1999.

Wang Z, Yunis D, Irigoyen M, Kitchens B, Bottaro A, Alt FW, Alper CA. Discordance between IgA switching at the DNA level and IgA expression at the mRNA level in IgA-deficient patients. Clin Immunol 91:263-70, 1999.

Seidl KJ, Manis JP, Bottaro A, Zhang J, Davidson L, Kisselgof A, Oettgen H, Alt FW. Position-dependent inhibition of class-switch recombination by PGK-neor cassettes inserted into the immunoglobulin heavy chain constant region locus. Proc Natl Acad Sci U S A 96:3000-5, 1999.

Sakai E, Bottaro A, Davidson L, Sleckman BP, Alt FW. Recombination and transcription of the endogenous Ig heavy chain locus is effected by the Ig heavy chain intronic enhancer core region in the absence of the matrix attachment regions. Proc Natl Acad Sci U S A 96:1526-31, 1999.