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Separate elements control DJ and VDJ rearrangement in a transgenic recombination substrate
P Ferrier1, B Krippl, T K Blackwell
1Howard Hughes Medical Institute, College of Physicians and Surgeons, Columbia University, New York, NY 10032.
The EMBO Journal
|January 1, 1990
Summary
Transgenic mice reveal key DNA elements controlling T cell receptor (TCR) gene rearrangement. The enhancer element initiates DNA rearrangement in lymphoid cells, while another element ensures T cell-specific complete gene assembly.
Area of Science:
- Immunology
- Molecular Biology
- Genetics
Background:
- T cell receptor (TCR) gene rearrangement is crucial for adaptive immunity.
- Understanding the cis-acting regulatory elements controlling TCR gene assembly is essential.
Purpose of the Study:
- To investigate the role of specific DNA elements in controlling T cell receptor beta (TCRβ) VDJ rearrangement.
- To identify regulatory elements responsible for lymphoid-specific and T cell-specific gene assembly.
Main Methods:
- Generation of transgenic mice carrying engineered TCR beta gene miniloci.
- Analysis of gene rearrangement frequencies in various tissues and cell types.
- Characterization of DNA segments, including the immunoglobulin heavy chain enhancer (Eμ).
Main Results:
- Transgenic constructs with the Eμ-containing segment showed high-frequency rearrangement in lymphoid tissues.
- The Eμ-containing segment facilitated partial TCR gene assembly (D to J) in both B and T cells.
- Complete TCR gene rearrangement (V to DJ) was exclusively observed in T cells.
Conclusions:
- A cis-acting element within the Eμ-containing DNA segment initiates lymphoid-specific TCR beta D to J rearrangement.
- A separate element confers T cell-specific control over complete V beta to DJ beta gene assembly.
- These findings elucidate distinct regulatory mechanisms governing TCR gene rearrangement.