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Table 1 Summary of currently available ATM, ATR and DNA-PKcs mouse models

From: ATM, ATR and DNA-PKcs kinases—the lessons from the mouse models: inhibition ≠ deletion

Mouse models Mutations Fitness Fertility Main phenotypes References
 DNA-PKcs/ Null/knockout Viable Fertile SCID; T and B cells developmental blockade; defective coding joint formation Taccioli et al. [188], Gao et al. [49]; Kurimasa et al. [50]
 DNA-PKcs3A/3A Knockin, T2605/T2634/T2643A, phosphorylation site mutations Viable ND Small; p53 dependent bone marrow failure; early lethality (2–3 weeks old) Zhang et al. [74]
 DNA-PKcsKD/KD and Knockin, kinase dead DNA-PKcs (D3922A) Embryonic lethal (E16.5) ND SJ and CJ fomation blocked; CSR defects; embryonic lethality rescued by KU deletion Jiang et al. [20], Crowe et al. [62]
 DNA-PKcsPQR/PQR Knockin, S2053 cluster mutated to Alanine Viable Fertile Normal CSR and V(D)J recombination; moderate IR sensitivity Jiang et al. [73]
 DNA-PKcsSD/SD Knockin, S2053 cluster mutated to Aspartate Viable Fertile Normal CSR and V(D)J recombination Jiang et al. [73]
 Atm/ Null/knockout Viable Infertile Growth retardation; lack of mature gametes; T cells deficiency and thymic lymphomas Barlow et al. [91], Elson et al. [92], Xu et al. [93], Borghesani et al. [94]
 AtmTgS1987A and AtmTgS1987A/S367A/S1899A BAC transgene, S1987A or S1987A/S367A/A1899A, phosphorylation site mutations Viable Fertile No major phenotypes; proper DDR Pellegrini et al. [99], Daniel et al. [100]
 AtmKD/KD and AtmKD/** Knockin, kinase dead ATM (D2880A, N2885K) Embryonic lethal (E9.5) ND Severe genomic instability; hyper sensitivity to Topoisomerase I inhibitors and pro-cancer Yamamoto et al. [18, 121]
 AtmTgD2899A Atm/and AtmTgQ2740P Atm/ BAC transgene, kinase dead ATM (D2899A, Q2740P) Embryonic lethal (< E12.5) ND Severe genomic instability, PARP inhibitor sensitivity Daniel et al. [19]
 Atr/ Null/knockout Embryonic lethal (< E7.5) ND Chromosome fragmentation at blastocyst stage Brown et al. [125]
de Klein et al. [146],
 AtrSeckel/Seckel Seckel mutation (exons 8–10 replaced by human sequence with A ≥ G substitution in exon 9) Viable Fertile Craniofacial abnormalities; growth retardation; embryonic replicative stress; accelerated aging Murga et al. [152]
 Atr +/KD Knockin, kinase dead ATR (D2466A) Viable Male infertility Male spermatogenesis defects, mild lymphocytopenia Menolfi et al. [21]
 AtrKD/*** Knockin, kinase dead ATR (D2466A) Embryonic lethal (< E9) ND Early embryonic lethality Menolfi et al. [21]
  1. ND not determined
  2. * DNA-PKcs+/− and DNA-PKcs+/KD mice are viable and fertile
  3. ** Atm+/− and Atm+/KD mice are viable and fertile
  4. *** Atr+/− mice are viable and fertile. AtrKD/KD mice cannot be obtained due to Atr+/KD male infertility