Ide Yasuhito, Tsuchimoto Daisuke, Tominaga Yohei, Nakashima Manabu, Watanabe Takeshi, Sakumi Kunihiko, Ohno Mizuki, Nakabeppu Yusaku
Division of Neurofunctional Genomics, Department of Immunobiology and Neuroscience, Medical Institute of Bioregulation, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812 8582, Japan.
Blood. 2004 Dec 15;104(13):4097-103. doi: 10.1182/blood-2004-04-1476. Epub 2004 Aug 19.
APEX2/APE2 is a secondary mammalian apurinic/apyrimidinic endonuclease that associates with proliferating cell nuclear antigen (PCNA), and the progression of S phase of the cell cycle is accompanied by its expression. To determine the biologic significance of APEX2, we established APEX2-null mice. These mice were about 80% the size of their wild-type littermates and exhibited a moderate dyshematopoiesis and a relatively severe defect in lymphopoiesis. A significant accumulation of both thymocytes and mitogen-stimulated splenocytes in G(2)/M phase was seen in APEX2-null mice compared with the wild type, indicating that APEX2 is required for proper cell cycle progression of proliferating lymphocytes. Although APEX2-null mice exhibited an attenuated immune response against ovalbumin in comparison with wild-type mice, they produced both antiovalbumin immunoglobulin M (IgM) and IgG, indicating that class switch recombination can occur even in the absence of APEX2.
APEX2/APE2是一种二级哺乳动物脱嘌呤/脱嘧啶内切酶，与增殖细胞核抗原（PCNA）相关联，并且细胞周期S期的进程伴随着其表达。为了确定APEX2的生物学意义，我们构建了APEX2基因敲除小鼠。这些小鼠的体型约为其野生型同窝小鼠的80%，表现出中度造血异常和相对严重的淋巴细胞生成缺陷。与野生型相比，在APEX2基因敲除小鼠中可见胸腺细胞和有丝分裂原刺激的脾细胞在G(2)/M期有显著积累，表明APEX2是增殖淋巴细胞正常细胞周期进程所必需的。尽管与野生型小鼠相比，APEX2基因敲除小鼠对卵清蛋白的免疫反应减弱，但它们产生了抗卵清蛋白免疫球蛋白M（IgM）和IgG，表明即使在没有APEX2的情况下也能发生类别转换重组。
