Abnormal V(D)J recombination of T cell receptor β locus in SMAR1 transgenic mice

Abstract

Scaffold/matrix-associated region-1-binding protein (SMAR1) specifically interacts with the MARβ sequence, which is located 400-bp upstream of the murine TCRβ 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 Vβs (Vβ5.1/5.2 and Vβ8.1/8.2/8.3). The rearrangements of Vβ5.1/5.2, Vβ8.1/8.2/8.3 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.