Shimoyama Manabu, Matsuoka Hiroshi, Nagata Aki, Iwata Nobuko, Tamekane Akira, Okamura Atsuo, Gomyo Hiroshi, Ito Mitsuhiro, Jishage Kou-ichi, Kamada Nobuo, Suzuki Hiroshi, Tetsuo Noda Tetsuo, Matsui Toshimitsu
Division of Hematology/Oncology, Department of Medicine, Kobe University School of Medicine, Chuo-ku, Kobe, Hyogo 650-0017, Japan.
Biochem Biophys Res Commun. 2002 Oct 18;298(1):87-94. doi: 10.1016/s0006-291x(02)02399-9.
A member of the largest family of receptor protein kinases, EphB6, lacks its intrinsic kinase activity, but it is expressed in normal human tissues. To investigate the physiological function of EphB6, we generated EphB6 deficient mice. EphB6(-/-) mice developed normally, revealed no abnormality in general appearance, and were fertile. Although a developmental increase of EphB6 in the fetal thymus was confirmed, T-cell development in various lymphoid organs of EphB6(-/-) mice was comparable to those of EphB6(+/+). Even in fetal thymus organ cultures, any developmental differences of EphB6(-/-) and EphB6(+/+) thymocytes were undetectable. The different binding characteristics to ephrin-Fc proteins between EphB6(-/-) and EphB6(+/+) thymocytes demonstrated that ephrin-B2 is the unique ligand for EphB6 among eight known ephrins. While EphB6 was a dominant receptor that binds to ephrin-B2 in adult thymocytes, fetal ones also expressed another EphB that binds to ephrin-B2. Overlapping expression of the EphB subfamily in the fetal thymus might compensate for the loss of EphB6 during the thymic development.
作为受体蛋白激酶最大家族的成员之一，EphB6缺乏其内在激酶活性，但在正常人体组织中表达。为了研究EphB6的生理功能，我们培育了EphB6基因敲除小鼠。EphB6(-/-)小鼠发育正常，外观无异常，且具有生育能力。虽然已证实在胎儿胸腺中EphB6会随着发育而增加，但EphB6(-/-)小鼠各种淋巴器官中的T细胞发育与EphB6(+/+)小鼠相当。即使在胎儿胸腺器官培养中，也未检测到EphB6(-/-)和EphB6(+/+)胸腺细胞之间存在任何发育差异。EphB6(-/-)和EphB6(+/+)胸腺细胞对ephrin-Fc蛋白的结合特性不同，这表明在八种已知的ephrin中，ephrin-B2是EphB6唯一的配体。虽然EphB6是成年胸腺细胞中与ephrin-B2结合的主要受体，但胎儿胸腺细胞也表达另一种与ephrin-B2结合的EphB。EphB亚家族在胎儿胸腺中的重叠表达可能补偿了胸腺发育过程中EphB6的缺失。
