The Journal of Experimental Medicine
Keystone Symposia
  Home | Help | Feedback | Subscriptions | Archive | Search | Table of Contents
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow PPT slides of all figures
Right arrow Alert me when this article is cited
Right arrow Citation Map
Services
Right arrow Email this article
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new content in the JEM
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via CrossRef
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Cocea, L.
Right arrow Articles by Reynaud, C.-A.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Cocea, L.
Right arrow Articles by Reynaud, C.-A.
Social Bookmarking
Add to CiteULike   Add to Complore   Add to Connotea   Add to Del.icio.us   Add to Digg   Add to Reddit   Add to Technorati  
What's this?

J. Exp. Med., Volume 189, Number 9, May 3, 1999 1443-1450

A Targeted Deletion of a Region Upstream from the Jkappa Cluster Impairs kappa  Chain Rearrangement In Cis in Mice and in the 103/bcl2 Cell Line

By Laurentiu Cocea,* Annie De Smet,* Mahasti Saghatchian,* Simon Fillatreau,* Laurent Ferradini,* Stéphane Schurmans,Dagger Jean-Claude Weill,* and Claude-Agnès Reynaud*

From the * Institut National de la Santé et de la Recherche Médicale, Unité 373, Faculté de Médecine Necker, Paris, France; and Dagger  Institut de Recherches Interdisciplinaires en Biologie Humaine et Nucleare (IRIBHN), Faculté de Médecine, Université Libre de Bruxelles, Bruxelles, Belgium

We have shown previously that a mutation of the KI-KII site immediately 5' to Jkappa 1 on the mouse immunoglobulin light chain kappa  locus reduces the rearrangement level in cis, although it does not affect transcription. Here we deleted by homologous recombination in mouse embryonic stem cells a 4-kb DNA fragment, located immediately upstream of the KI-KII element, which contains the promoter of the long germline transcript. Analysis of gene-targeted heterozygous mouse splenic B cells showed a strong decrease in rearrangement for the allele bearing the deletion. When both the KI-KII mutation and the 4-kb deletion were present on the same allele, the overall reduction in rearrangement was stronger than with the 4-kb deletion alone underlying the role of these two elements in the regulation of rearrangement. The same deletion was performed by homologous recombination on one allele of the rearrangement- inducible mouse 103/bcl2-hygroR pre-B cell line, and resulted in a similar reduction in the induction of rearrangement of the mutated allele. This result validates this cell line as an in vitro model for studying the incidence of gene-targeted modifications of the kappa  locus on the regulation of rearrangement.

Key words: regulation of rearrangement;  mouse immunoglobulin genes;  allelic exclusion;  germline promoter;  positive regulatory element


Add to CiteULike CiteULike   Add to Complore Complore   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us   Add to Digg Digg   Add to Reddit Reddit   Add to Technorati Technorati    What's this?


This article has been cited by other articles:



  Home | Help | Feedback | Subscriptions | Archive | Search
TABLE OF CONTENTS