Protective effects of inactive Adar1 protein and mutations reducing cell death in Adar mutant mouse pups
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| Year of publication | 2023 |
| Type | Conference abstract |
| MU Faculty or unit | |
| Citation | |
| Description | The AdarE861A mutant encoding catalytically inactive Adar1 RNA editing enzyme is embryonic lethal but embryos survive 2 days longer than embryo with the Adar?2-13 null mutant. We made strains to compare rescues in Adar?2-13 null and AdarE861A catalytically inactive mutant backgrounds when either Mda5 or Mavs are also removed and aberrant interferon induction by unedited endogenous dsRNA is prevented. As a result of these crosses, we generated many AdarE861A Mavs double homozygous mice, which are near normal size, suggesting a pretty complete rescue by removing Mavs. We also generated AdarE861A IfiH1 (Mda5) double mutant mice that appear fully rescued and reach breeding age. We are investigating the role of AdarE861A in intestinal apoptosis, which occurs in Adar?2-13 Mavs double homozygous pups but should not occur in the AdarE861A Mavs double mutant. Double mutant mice with AdarE861A and either Mavs or Ifih1 mutations appear well rescued. However, when we use Adar E861A IfiH1 (Mda5) or Adar E861A Mavs double homozygous mutant female mice in crosses, all the progeny are small and die early. This is the case not only when the pups have the same Adar E861A IfiH1 (Mda5) or Adar E861A /Mavs double mutant genotype as the mother but even if they are heterozygous for AdarE861A. Therefore, there is a severe maternal defect in the Adar E861A IfiH1 or Adar E861A Mavs double homozygous others. Unpublished reports suggest that Adar knockout in endothelial cells of blood vessels recapitulates the severe blood-related defects seen in whole embryo Adar null mutants; therefore, the AdarE861A / E861A IfiH1- /- mothers might have placental insufficiency due to defects in placental blood vessel development. For this reason, we are examining placentae of at E18.5- E19.5 fetuses in all crosses to explain maternal effect on development of pups. |
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