Effect of RNAseH2a mutation on INDEL frequency in zebrafish genome
Removal of ribonucleotides from DNA by RNaseH2 is essential for genome stability. Impaired function of this complex is a driver of the neurodegenerative disease, Aicardi Goutières Syndrome. We have created a zebrafish rnash2a mutant to model this process. Surprisingly, RNaseH2a knockouts show little phenotypic abnormality at adulthood, unlike previous mouse knockout models, which are early embryonic lethal. However, their offspring show reduced development, increased ribonucleotide incorporation and upregulation of key inflammatory markers, resulting in both maternal and paternal embryonic lethality. Despite their survival, rnaseh2a-/- adults show an accumulation of ribonucleotides in both the brain and testes that is not present in early development. We studied whther lack of RnasH2a has effects on the level of INDELs in the genome of a homozyote vs wildtype animals