Disruption of ZAS3 in Mice Alters NF-κB and AP-1 DNA Binding and T-Cell Development
Year: 2007
Type: article
Abstract: The large zinc finger proteins, ZAS, regulate the transcription of a variety of genes involved in cell growth, development, and metastasis. They also function in the signal transduction of the TGF-beta and TNF-alpha pathways. However, the endogenous protein of a representative member, ZAS3, is rapidly degraded in primary lymphocytes, which limits the determination of its physiological function in vitro. Therefore, we have generated mice with targeted disruption of ZAS3. Oligonucleotide-based microarray analyses revealed subtle but consistent differences in the expression of genes, many of which are associated with receptor or signal transduction activities between ZAS3+/+ and ZAS3-/- thymi. Gel mobility shift assays showed altered DNA binding activities of NF-kappaB and AP-1 proteins in ZAS3-deficient tissues, including the thymus. Lymphocyte analysis suggested a subtle but broad function of ZAS3 in regulating T-cell development and activation. In CD3+ ZAS3-/- thymocytes, the CD4/ CD8 ratio was decreased and CD69 expression was decreased. In peripheral CD4+ ZAS3-/- lymphocytes we observed an increased number of memory T cells.
Source: Gene Expression
Authors: CARL E. ALLEN, JOHN RICHARDS, NATARAJAN MUTHUSAMY, HERBERT AUER, YANG LIU, MICHAEL L. ROBINSON, JOHN A. BARNARD, LAI-CHU WU
Institution: Abigail Wexner Research Institute
Language: English
Topic: T-cell and B-cell Immunology
Subfield: Immunology
Field: Immunology and Microbiology
Domain: Life Sciences
Open Access status: hybrid
OpenAlex ID: W2053353511