By Frank J. Dixon
The Scripps examine Institute, los angeles Jolla, CA. most modern findings within the box of immunology. converted define layout.
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Extra resources for Advances in Immunology, Vol. 69
A potential problem of this experimental approach was the fact that pTa’ and pTa-’chimeric mice were not of the same transgenic background, as they were generated from pTa+/- and pTa? ES cell clones that had been transfected individually with the respective TCRP transgene, almost certainly giving rise to animals with distinct transgene copy numbers and/or insertion sites. , 1996). The opposite conclusion was reached in a subsequent study using stable lines of pTa? and TCRP-transgenic, pTa-’- mice rather than chimeric animals, which permitted a more rigorous analysis.
Under these conditions (complete absence of allelic exclusion), it MOLECULAR AND CELLULAR EVENTS IN THYMOCYTE DEVELOPMENT 41 was calculated (see Fig. 3) that 20% of TCRP positive cells would express two distinct /3 chains. Any, even partial, violation of these assumptions would reduce the percentage of double expressing cells. Given the low frequency of cells that express a particular VP element in normal, nontransgenic mice, it was clear that evidence for incomplete allelic exclusion would not be easy to obtain by cell surface staining with antibodies specific for just two different VP elements.
Because TCRa rearrangements occur significantly after TCRP, 6 and y rearrange- MOLECULAR AND CELLULAR EVENTS IN THYMOCYTE DEVELOPMENT 37 ments, radiation-induced restoration of V( D)J recombination appears to be temporally restricted. Taken together, these findings strongly suggest that y irradiation of SCID mice induces a DNA repair pathway that can transiently compensate for the SCID defect in V(D)J recombination, leading to normal TCRP expression, formation of a pre-TCR, and generation of DP thymocytes in a pre-TCR-dependent fashion.
Advances in Immunology, Vol. 69 by Frank J. Dixon