Division of Cellular and Molecular Biology, Institute of Medical Science, University of Tokyo, 4-6-1 Shirokane-dai, Minato-ku, Tokyo 108-8639, Japan.
Biochem Biophys Res Commun. 2011 Nov 4;414(4):773-8. doi: 10.1016/j.bbrc.2011.10.001. Epub 2011 Oct 7.
NF-κB-inducing kinase (NIK) plays critical roles in the development of lymph nodes and Peyer's patches, and microarchitecture of the thymus and spleen via NF-κB activation. Alymphoplasia (aly/aly) mice have a point mutation in the NIK gene that causes a defect in the activation of an NF-κB member RelB. Here, we developed a novel method to determine the aly mutation by genetic typing using PCR. This method facilitated the easy establishment of a congeneic aly/aly mouse line. Indeed, we generated a mouse line with aly mutation on a BALB/cA background (BALB/cA-aly/aly). BALB/cA-aly/aly mice showed significant splenomegaly with extramedullary hemopoiesis, which was not significant in aly/aly mice on a C57BL/6 background. Interestingly, the splenomegaly and extramedullary hemopoiesis caused by the aly mutation was gender-dependent. These data together with previous reports on extramedullary hemopoiesis in RelB-deficient mice suggest that NIK-RelB signaling may be involved in the suppression of extramedullary hemopoiesis in adult mice.
NF-κB 诱导激酶 (NIK) 通过 NF-κB 的激活，在淋巴结和派尔氏斑、胸腺和脾脏的微结构发育中发挥关键作用。无浆细胞发育不良（aly/aly）小鼠的 NIK 基因发生点突变，导致 NF-κB 成员 RelB 的激活缺陷。在这里，我们开发了一种使用 PCR 通过遗传分型确定 aly 突变的新方法。这种方法有助于轻松建立同源 aly/aly 小鼠系。事实上，我们在 BALB/cA 背景下生成了带有 aly 突变的小鼠系（BALB/cA-aly/aly）。BALB/cA-aly/aly 小鼠表现出明显的脾肿大伴骨髓外造血，而在 C57BL/6 背景下的 aly/aly 小鼠中则不明显。有趣的是，aly 突变引起的脾肿大和骨髓外造血具有性别依赖性。这些数据与 RelB 缺陷型小鼠骨髓外造血的先前报告一起表明，NIK-RelB 信号通路可能参与抑制成年小鼠的骨髓外造血。
