Essential Role for the Lymphostromal Plasma Membrane Ly-6 Superfamily Molecule Thymic Shared Antigen 1 in Development of the Embryonic Adrenal Gland

Thymic shared antigen 1 (TSA-1) is a plasma membrane protein of the Ly-6 superfamily expressed on thymocytes, thymic stromal cells, and other cells of the hematopoietic system. TSA-1 is also expressed in other nonhematopoietic tissues, in particular, embryonic and adult adrenal glands. To address the function of TSA-1, we generated mutant mice in which TSA-1 expression was inactivated by gene targeting. Here we show that deletion of both TSA-1 alleles results in abnormal adrenal gland development and midgestational lethality due to cardiac abnormalities. We also report that TSA-1-deficient adrenal glands have significantly reduced levels of the catecholamines noradrenaline and adrenaline. We conclude that TSA-1 is required for normal embryonic development but that deletion of its expression does not obviously impair lymphoid development.

胸腺共同抗原1（Thymic shared antigen 1，TSA-1）属于Ly-6超家族的质膜蛋白，可表达于胸腺细胞、胸腺基质细胞及造血系统的其他多种细胞。TSA-1亦可在其他非造血组织中表达，尤以胚胎与成年肾上腺组织为著。为阐明TSA-1的生物学功能，我们通过基因靶向技术构建了TSA-1表达失活的突变小鼠模型。本研究证实，TSA-1等位基因纯合缺失会导致肾上腺发育异常，并因心脏缺陷引发妊娠中期致死。我们同时发现，TSA-1缺陷小鼠的肾上腺组织中，儿茶酚胺类物质去甲肾上腺素与肾上腺素的水平显著降低。综上，TSA-1对于正常胚胎发育是必需的，但该基因的表达缺失并未明显损害淋巴系统发育。