Boucher Didier, Vu Therese, Bain Amanda L, Tagliaro-Jahns Marina, Shi Wei, Lane Steven W, Khanna Kum Kum
*Signal Transduction Laboratory, Translational Leukaemia Research, QIMR Berghofer Medical Research Institute, Herston, Queensland, Australia; University of Queensland, Brisbane, Queensland, Australia; Institut National De La Recherche Agronomique, Institut Jean-Pierre Bourgin, Unité Mixte de Recherche 1318, Équipes de Recherche Labellisées Centre National de la Recherche Scientifique 3559, Saclay Plant Sciences, Versailles, France.
*Signal Transduction Laboratory, Translational Leukaemia Research, QIMR Berghofer Medical Research Institute, Herston, Queensland, Australia; University of Queensland, Brisbane, Queensland, Australia; Institut National De La Recherche Agronomique, Institut Jean-Pierre Bourgin, Unité Mixte de Recherche 1318, Équipes de Recherche Labellisées Centre National de la Recherche Scientifique 3559, Saclay Plant Sciences, Versailles, France
FASEB J. 2015 Aug;29(8):3326-34. doi: 10.1096/fj.14-269944. Epub 2015 Apr 27.
SSB1 and SSB2 are newly identified single-stranded (ss) DNA binding proteins that play a crucial role in genome maintenance in humans. We recently generated a knockout mouse model of Ssb1 and revealed its essential role for neonatal survival. Notably, we found compensatory up-regulation of Ssb2 protein levels in multiple tissues of conditional Ssb1(-/-) mice, suggesting functional compensation between these 2 proteins. We report here the first description of Ssb2(-/-) knockout mice. Surprisingly, unlike Ssb1 knockout mice, Ssb2(-/-) mice are viable and fertile and do not exhibit marked phenotypic changes when compared with their Ssb2(+/+) and Ssb2(+/-) littermates. Notably, we did not detect any pathologic changes in the thymus, spleen, or testes, tissues with the most abundant expression of Ssb2. Moreover, Ssb2(-/-) mouse embryonic fibroblasts (MEFs) did not show any sensitivity to DNA-damaging agents, or defects in DNA repair capacity. However, we observed modest up-regulation of Ssb1 levels in Ssb2(-/-) MEFs as well as in Ssb2(-/-) thymus and spleen, suggesting that Ssb1 is likely able to compensate for the loss of Ssb2 in mice. Altogether, our results show that Ssb2 is dispensable for embryogenesis and adult tissue homeostasis, including thymopoiesis, splenic development, male fertility, and DNA repair in mice.
SSB1和SSB2是新发现的单链（ss）DNA结合蛋白，在人类基因组维持中发挥关键作用。我们最近构建了Ssb1基因敲除小鼠模型，并揭示了其对新生小鼠存活的重要作用。值得注意的是，我们发现条件性Ssb1（-/-）小鼠多个组织中Ssb2蛋白水平有代偿性上调，提示这两种蛋白之间存在功能代偿。我们在此首次报道了Ssb2（-/-）基因敲除小鼠。令人惊讶的是，与Ssb1基因敲除小鼠不同，Ssb2（-/-）小鼠可存活且可育，与它们的Ssb2（+/+）和Ssb2（+/-）同窝小鼠相比，未表现出明显的表型变化。值得注意的是，我们在Ssb2表达最丰富的胸腺、脾脏或睾丸组织中未检测到任何病理变化。此外，Ssb2（-/-）小鼠胚胎成纤维细胞（MEF）对DNA损伤剂未显示出任何敏感性，也没有DNA修复能力缺陷。然而，我们观察到Ssb2（-/-）MEF以及Ssb2（-/-）胸腺和脾脏中Ssb1水平有适度上调，提示Ssb1可能能够代偿小鼠中Ssb2的缺失。总之，我们的结果表明，Ssb2对于小鼠胚胎发育和成年组织稳态（包括胸腺生成、脾脏发育、雄性生育能力和DNA修复）是可有可无的。
