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J. Biol. Chem., Vol. 280, Issue 10, 9450-9459, March 11, 2005

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Abnormal V(D)J Recombination of T Cell Receptor Locus in SMAR1 Transgenic Mice^*

Ruchika Kaul-Ghanekar, Subeer Majumdar, Archana Jalota, Neerja Gulati, Neetu Dubey, Bhaskar Saha, and Samit Chattopadhyay¶

From the National Center for Cell Science, Pune University Campus, Ganeshkhind, Pune 411007 and National Institute of Immunology, Aruna Asaf Ali Marg, New Delhi 100067, India

Scaffold/matrix-associated region-1-binding protein (SMAR1) specifically interacts with the MAR sequence, which is located 400-bp upstream of the murine TCR enhancer and is highly expressed during the DP stage of thymocyte development. To further analyze the functions of SMAR1, transgenic mice were generated that express SMAR1 in a tissue-independent manner. SMAR1-overexpressing mice exhibit severely altered frequency of the T cells expressing commonly used Vs (V5.1/5.2 and V8.1/8.2/8.3). The rearrangements of V5.1/5.2, V8.1/8.2/8.3 loci are also reduced in SMAR1 transgenic mice. The T cells in SMAR1 transgenic mice exhibit a mild perturbation at the early DN stage. SMAR1 transgenic mice exhibit hypercellular lymph nodes and spleen accompanied with prominent architectural defects in these organs. These results indicate that SMAR1 plays an important role in the regulation of T cell development as well as V(D)J recombination besides maintaining the architecture of the lymphoid organs.

Received for publication, October 28, 2004 , and in revised form, December 21, 2004.

^* This work was supported by grants from the Department of Science and Technology and Department of Biotechnology, New Delhi, India. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

^¶ To whom correspondence should be addressed. Tel.: 91-20-569-0922; Fax: 91-20-569-2259; E-mail: samit{at}nccs.res.in.

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