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The phenotype of the most common human ADAR1p150 Za mutation P193A in mice is partially penetrant


ABSTRACT: ADAR1 mediated A-to-I RNA editing is a self/non-self discrimination mechanism for cellular double stranded RNAs. ADAR mutations are one cause of Aicardi-Goutières Syndrome, an inherited paediatric encephalopathy, classed as a "Type I interferonopathy". The most common ADAR1 mutation is a proline 193 alanine (p.P193A) mutation, mapping to the ADAR1p150 isoform specific Z domain. Here we report the development of an independent murine P195A knock-in mouse, homologous to human P193A. The Adar1P195A/P195A mice are largely normal and the mutation is well tolerated. When the P195A mutation is compounded with an Adar1 null allele (Adar1P195A/-), approximately half the animals are runted with a shortened lifespan while the remaining Adar1P195A/- animals are normal, contrasting with previous reports. The phenotype of the Adar1P195A/- animals is both associated with the parental genotype and partly non-genetic/environmental. Complementation with an editing deficient ADAR1 (Adar1P195A/E861A), or the loss of MDA5, rescues phenotypes in the Adar1P195A/- mice.

SUBMITTER: Ms. Zhen Liang 

PROVIDER: S-SCDT-10_15252-EMBR_202255835 | biostudies-other |

REPOSITORIES: biostudies-other

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