Strain Data Sheet
RBRC10696
Strain Information | |
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| Image | |
| BRC No. | RBRC10696 |
| Type | Targeted Mutation |
| Species | Mus musculus |
| Strain name | B6.129P2-Aplf<tm1Okad> |
| Former Common name | Aplf KO |
| H-2 Haplotype | |
| ES Cell line | E14K [129P2/OlaHsd] |
| Background strain | |
| Appearance | |
| Strain development | B6.129P2-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 description | Aprataxin 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 | |
| References | Attenuated DNA damage repair delays therapy-related myeloid neoplasms in a mouse model. Tong K I, Ota K, Komuro A, Ueda T, Ito A, Anne Koch C, Okada H Cell Death Dis., 7(10):e2401 (2016). 27711078 |
Health Report | |
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| Examination Date / Room / Rack | |
Gene | |||||||
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| Gene Symbol | Gene Name | Chr. | Allele Symbol | Allele Name | Common Names | Promoter | Diseases Related to This Gene |
| Aplf | aprataxin and PNKP like factor | 6 | Aplf | targeted mutation 1, Hitoshi Okada | |||
| neo | neomycin resistance gene (E. coli) | 6 | mouse phosphoglycerate kinase promoter (PGK promoter) | ||||
Phenotype | |
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| Annotation by Mammalian phenotyhpe ontology | |
| Detailed phenotype data | |
Ordering Information | |
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| Donor DNA | mouse PGK promoter, E. coli neomycin resistance gene, mouse polyA additional signal, mouse Aplf genomic DNA |
| Research application | |
| Specific Term and Conditions | Prior to requesting the BIOLOGICAL RESOURCE, the RECIPIENT must obtain approval from the DEPOSITOR using the Approval Form. |
| Depositor | Hitoshi Okada (Kindai University) |
| Strain Status |  Frozen sperm |
| Strain Availability | Recovered litters from cryopreserved sperm (2 to 4 months) Cryopreserved sperm (within 1 month) |
| Additional Info. | Necessary documents for ordering:
Genotyping protocol -PCR- |
BRC mice in Publications |
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| No Data |