Ssb2/Nabp1 is dispensable for thymic maturation, male fertility, and DNA repair in mice.
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.
*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.
Didier
D
Boucher
*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.
Therese
T
Vu
*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.
Amanda L
AL
Bain
*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.
Marina
M
Tagliaro-Jahns
*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.
Wei
W
Shi
*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.
Steven W
SW
Lane
*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 kumkum.khanna@qimrberghofer.edu.au.
Kum Kum
KK
Khanna
D000818:Animals; D002352:Carrier Proteins / Q000378:metabolism*; D004260:DNA Repair / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000378:metabolism*; D005298:Fertility / Q000235:genetics*; D005347:Fibroblasts / Q000378:metabolism / Q000502:physiology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D011485:Protein Binding / Q000235:genetics; D013154:Spleen / Q000378:metabolism / Q000502:physiology; D013950:Thymus Gland / Q000378:metabolism* / Q000502:physiology; D015854:Up-Regulation / Q000235:genetics
D002352:Carrier Proteins; D004268:DNA-Binding Proteins; C511297:NABP1 protein, mouse
DNA damage response; knockout mouse model; testis development; thymopoiesis