| Experiment Id | GSE220628 | Name | The phenotype of the most common human ADAR1p150 Za domain mutation P193A in mice is incompletely penetrant |
| Experiment Type | RNA-Seq | Study Type | WT vs. Mutant |
| Source | GEO | Curation Date | 2023-08-05 |
| description | 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-Goutieres 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 Za domain. We report the development of an independent murine P195A knock-in mouse, homologous to the human P193A mutation. The Adar1P195A/P195A mice are largely normal and the mutation is well tolerated. Contrasting with previous reports when the P195A mutation was compounded with an ADAR1 null allele (Adar1P195A/-), we find a partially penetrant phenotype, with approximately half the animals being runted with a shortened lifespan and the remaining animals normal. Severe runting and shortened survival of Adar1P195A/- animals were partly associated with the parental genotype. The P195A mutation is well tolerated in vivo and the loss of MDA5 is sufficient to completely rescue phenotypes in the Adar1P195A/- mice. Whole brain from 3-4 replicates of each genotype were subjected to RNA sequencing. |
