Growth retardation and dyslymphopoiesis accompanied by G2/M arrest in APEX2-null mice.
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.
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.
Yasuhito
Y
Ide
Daisuke
D
Tsuchimoto
Yohei
Y
Tominaga
Manabu
M
Nakashima
Takeshi
T
Watanabe
Kunihiko
K
Sakumi
Mizuki
M
Ohno
Yusaku
Y
Nakabeppu
D000818:Animals; D000831:Animals, Newborn; D001284:Atrophy; D002455:Cell Division / Q000276:immunology*; D017931:DNA Primers; D043603:DNA-(Apurinic or Apyrimidinic Site) Lyase; D004720:Endonucleases / Q000172:deficiency* / Q000235:genetics / Q000502:physiology; D016195:G2 Phase / Q000276:immunology*; D006128:Growth / Q000276:immunology*; D006410:Hematopoiesis / Q000235:genetics / Q000276:immunology; D008214:Lymphocytes / Q000166:cytology / Q000276:immunology; D038041:Lymphopoiesis / Q000235:genetics*; D051379:Mice; D018345:Mice, Knockout; D064251:Multifunctional Enzymes; D016133:Polymerase Chain Reaction; D013154:Spleen / Q000276:immunology; D013950:Thymus Gland / Q000473:pathology
D017931:DNA Primers; D064251:Multifunctional Enzymes; C476886:Apex2 protein, mouse; D004720:Endonucleases; D043603:DNA-(Apurinic or Apyrimidinic Site) Lyase