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The D-limited Mouse : a globally altered antibody repertoire shaped by the principle of CDR3 hydropathicity

by Gregory C Ippolito

  Thesis/dissertation : Thesis/dissertation : Manuscript   Archival Material

Evolutionary conservation of IgH D gene segments   (2009-10-08)

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by DFL16.1

Gene targeted mice were made wherein the IgH locus of germline D gene segments (~ 80 kb) was deleted by Cre-loxP engineering in ES cells.  The locus was replaced by a single D gene element -- either germline DFL16.1 (encoding Tyr, Ser, and Gly) or an inverted DFL16.1 (encoding the charged residues Arg and His and Asp).  This was sufficient to globally alter CDR-H3 sequence repertoire, to significantly perturb B-cell development, and resulted in impaired B-cell function and antibody production.  

The work in this dissertation has been published.

<a style="color: #551a8b;" href="">Forced usage of positively charged amino acids in immunoglobulin CDR-H3 impairs B cell development and antibody production.</a>

Ippolito GC, Schelonka RL, Zemlin M, Ivanov II, Kobayashi R, Zemlin C, Gartland GL, Nitschke L, Pelkonen J, Fujihashi K, Rajewsky K, Schroeder HW Jr.

J Exp Med. 2006 Jun 12;203(6):1567-78. Epub 2006 Jun 5.

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