RBRC10696

Information1

Image
BRC No.RBRC10696
TypeTargeted MutationCartagena
SpeciesMus musculus
Strain nameB6.129P2-Aplf<tm1Okad>
Former Common nameAplf KO
H-2 Haplotype
ES Cell lineE14K [129P2/OlaHsd]
Background strain
Appearance
Strain developmentB6.129P2-Aplf<tm1Okad> has been established by H Okada. ES cell: 129/OlaBackcrossed to C57BL/6J including B6 male more than 10 times.Aplf-/- mice are viable with no gross abonormality and grow normally. Both male and female Aplf-/- mice are fertile. We have maintained the mouse colony by backcrossing Aplf+/- with B6J since previous reports suggested a functional link between Aplf and telomere function; however, several crosses between homozygotes did not affect fertility. Cellularity of B cell was slightly lower than wild-type mice. Aplf-/- mice showed moderately impaired C-NHEJ activity. Thus, irradiated mutant mice showed higher rates of p53-dependent cell death and fewer chromosomal translocations.
Strain descriptionAprataxin and PNKP-like factor (APLF, also referred to as Xip1, C2orf13, and PALF) is a poly(ADP-ribose) or PAR-binding protein that interacts with C-NHEJ repair factors, XRCC4-DNA ligase 4 and Ku, to facilitate C-NHEJ in a PAR polymerase 3 (PARP3)-dependent manner. APLF can undergo ATM- and PARP3-dependent phosphorylation at serine-116 following ionizing radiation (IR), which is critical for the recruitment of APLF to the sites of DNA lesion to resolve γH2AX DNA damage signals. Accumulation of APLF to DSBs has been demonstrated to promote the retention of XRCC4/DNA ligase 4 complex in chromatin to facilitate DNA ligation during C-NHEJ. Furthermore, a phospho-ablative mutant of APLF (APLFS116A), which disabled IR-induced phosphoryation at serine-116 of APLF, exhibited higher persistent γH2AX DNA damage signal and lower cellular survival in colony formation assays after IR exposure reminiscent of cells with APLF depletion. These data suggest that APLF works downstream of ATM and PARP3 to modulate C-NHEJ after IR treatment. A moderate reduction of C-NHEJ activity by the depletion of APLF impedes radiation-induced oncogenic translocation in normal tissues and malignancy-associated mortality.
Colony maintenance
ReferencesCell Death Dis., 7(10):e2401 (2016). 27711078

Health Report

Examination Date / Room / RackNo Data

Gene

Gene info
Gene symbolGene nameChr.Allele symbolAllele namePromoter
Aplfaprataxin and PNKP like factor6Aplf<tm1Okad>

Gene symbolGene nameChr.Allele symbolAllele namePromoter
neoneomycin resistance gene (E. coli)6mouse phosphoglycerate kinase promoter (PGK promoter)

Information2

Donor DNAmouse PGK promoter, E. coli neomycin resistance gene, mouse polyA additional signal, mouse Aplf genomic DNA
Research application
Specific Term and ConditionsPrior to requesting the BIOLOGICAL RESOURCE, the RECIPIENT must obtain approval from the DEPOSITOR using the Approval Form.
DepositorHitoshi Okada (Kindai University)
Strain Statusan icon for Frozen spermFrozen sperm
Strain AvailabilityRecovered litters from cryopreserved sperm (2 to 4 months)
Cryopreserved sperm (within 1 month)
Additional Info.

BRC mice in Publications

No Data