4.7 Article

Important Functional Roles of Basigin in Thymocyte Development and T cell Activation

Journal

INTERNATIONAL JOURNAL OF BIOLOGICAL SCIENCES
Volume 10, Issue 1, Pages 43-52

Publisher

IVYSPRING INT PUBL
DOI: 10.7150/ijbs.6818

Keywords

Basigin; Cre-Loxp; gene targeting; thymocyte development; T cell activation

Funding

  1. China National Basic Research Program [2009CB521704]
  2. China National Key Project of Scientific and Technical Supporting Programs [2006BAI23B02]
  3. Key Project of China National Natural Science Fund [81030058]
  4. China National Major Project [2013ZX09301301]
  5. National Science and Technology Major Projects [2012AA020806]
  6. China National Natural Science Foundation [30800573]

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Basigin is a highly glycosylated transmembrane protein that is expressed in a broad range of tissues and is involved in a number of physiological and pathological processes. However, the in vivo role of basigin remains unknown. To better understand the physiological and pathological functions of basigin in vivo, we generated a conditional null allele by introducing two loxP sites flanking exons 2 and 7 of the basigin gene (Bsg). Bsg(fl/fl) mice were born at the expected Mendelian ratio and showed a similar growth rate compared with wildtype mice. After crossing these mice with Lck-Cre transgenic mice, basigin expression was specifically inactivated in T cells in the resulting Lck-Cre; Bsg(fl/fl) mice. Although the birth and growth rate of Lck-Cre; Bsg(fl/fl) mice were similar to control mice, thymus development was partially arrested in Lck-Cre; Bsg(fl/fl) mice, specifically at the CD4(+)CD8(+) double-positive (DP) and CD4 single-positive (CD4(+)CD8(-), CD4SP) stages. In addition, CD4+ T cell activation was enhanced upon Concanavalin A (Con A) or anti-CD3/anti-CD28 stimulation but not upon PMA/Ionomycin stimulation in the absence of basigin. Overall, this study provided the first in vivo evidence for the function of basigin in thymus development. Moreover, the successful generation of the conditional null basigin allele provides a useful tool for the study of distinct physiological or pathological functions of basigin in different tissues at different development stages.

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