Characterization of PARP3 mice after experimental hypoxic-ischemic brain damage and behavioral studies
Poly (ADP-ribose) polymerases (PARPs) transfer ADP-ribose units from NAD+ to form a ramified polymer. PARP1, PARP2 and PARP3 are DNA-dependent PARPs that localize to DNA damage and synthesize poly ADP-ribose (PAR) covalently attached to target proteins. PARP1 is involved in the repair of both single-strand and double-strand breaks (SSBs and DSBs) and influences multiple repair pathways, including base excision repair (BER), homologous recombination (HR), alternative non-homologous end-joining (a-NHEJ) and nucleotide excision repair (NER). Less is know about PARP2 and PARP3 involvement in DNA repair. PARP3 is activated by DNAs containing DSBs, consistent with its role in DSB repair. Further details of the PARP2 and PARP3 DNA-dependent mechanisms of activation are needed to understand how these PARPs can play specific roles in repair pathways as part of the cellular response to DNA damage.
The aim of this study is to unravel the biological significance of PARP3 in neuroprotection in the brain.
The stress on mice used in behavioral studies will be very low. Mice tested in the T-maze will be food restricted. However, if they reach 85% of their original weight, they will be excluded from the test and again get unlimited access to food and water. The perinatal hypoxia-ischemia (HI) model is well established and has been used for many years in our lab. We believe that this method will give moderate strain to the mice. All experiments will be performed by persons who have great experience with the different methods, which will reduce the stress on the animals.
We plan to use a PARP3 KO mouse model, already available at KPM Rikshospitalet. C57BL/6N mice will be used as wild type controls. In total, we apply for 1460 mice (730 of each genotype).
We wish to study dynamic processes involved in behavior and hypoxic-ischemic brain damage. Thus, cell cultures cannot be used to answer our questions. The mouse genome can be easily modified and KO mice are therefore an important tool to study protein function both in healthy and sick animals. Further, the mouse and human genomes have 95% similarity and studies done in mice will therefore in many cases give answers that can be transferred to humans. To reduce the number of mice we will breed homozygous mice and use the same animals for different behavior tests.
The project is a continuation of project # 7261.
The aim of this study is to unravel the biological significance of PARP3 in neuroprotection in the brain.
The stress on mice used in behavioral studies will be very low. Mice tested in the T-maze will be food restricted. However, if they reach 85% of their original weight, they will be excluded from the test and again get unlimited access to food and water. The perinatal hypoxia-ischemia (HI) model is well established and has been used for many years in our lab. We believe that this method will give moderate strain to the mice. All experiments will be performed by persons who have great experience with the different methods, which will reduce the stress on the animals.
We plan to use a PARP3 KO mouse model, already available at KPM Rikshospitalet. C57BL/6N mice will be used as wild type controls. In total, we apply for 1460 mice (730 of each genotype).
We wish to study dynamic processes involved in behavior and hypoxic-ischemic brain damage. Thus, cell cultures cannot be used to answer our questions. The mouse genome can be easily modified and KO mice are therefore an important tool to study protein function both in healthy and sick animals. Further, the mouse and human genomes have 95% similarity and studies done in mice will therefore in many cases give answers that can be transferred to humans. To reduce the number of mice we will breed homozygous mice and use the same animals for different behavior tests.
The project is a continuation of project # 7261.