Protective effects of inactive Adar1 protein and mutations
reducing cell death in Adar mutant mouse pups

a 2023

Protective effects of inactive Adar1 protein and mutations reducing cell death in Adar mutant mouse pups

MELICHEROVÁ, Janka; Pavla MUSILOVÁ; Liam KEEGAN a Mary Anne O'CONNELL

Základní údaje

Originální název

Protective effects of inactive Adar1 protein and mutations reducing cell death in Adar mutant mouse pups

Autoři

MELICHEROVÁ, Janka; Pavla MUSILOVÁ ; Liam KEEGAN a Mary Anne O'CONNELL

Vydání

2023

Další údaje

Jazyk

angličtina

Typ výsledku

Konferenční abstrakt

Stát vydavatele

Rakousko

Utajení

není předmětem státního či obchodního tajemství

Označené pro přenos do RIV

Organizační jednotka

Přírodovědecká fakulta

Klíčová slova česky

Adar, RNA, Placenta, Survival

Klíčová slova anglicky

Adar, RNA, Placenta, Survival

Změněno: 5. 3. 2025 08:39, Mgr. Janka Melicherová

Anotace

V originále

The AdarE861A mutant encoding catalytically inactive Adar1 RNA editing enzyme is embryonic lethal but embryos survive 2 days longer than embryo with the AdarΔ2-13 null mutant. We made strains to compare rescues in AdarΔ2-13 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 AdarΔ2-13 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 Unpublished reports suggest that Adar knockout in endothelial cells of blood vessels recapitulates the severe blood-related defects seen in whole embryo Adar null mutants;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.

Návaznosti

GA19-16963S, projekt VaV

Název: Genetický model myši pro studium kontroly interferonu a zánětu

Investor: Grantová agentura ČR, A mouse genetic model to study the control of interferon and inflammation

Citovat

MELICHEROVÁ, Janka; Pavla MUSILOVÁ; Liam KEEGAN a Mary Anne O'CONNELL. Protective effects of inactive Adar1 protein and mutations reducing cell death in Adar mutant mouse pups. 2023.

@proceedings{2481758,
   author = {Melicherová, Janka and Musilová, Pavla and Keegan, Liam and O'Connell, Mary Anne},
   keywords = {Adar, RNA, Placenta, Survival},
   language = {eng},
   title = {Protective effects of inactive Adar1 protein and mutations reducing cell death in Adar mutant mouse pups},
   year = {2023}
}

TY  - CONF
ID  - 2481758
AU  - Melicherová, Janka - Musilová, Pavla - Keegan, Liam - O'Connell, Mary Anne
PY  - 2023
TI  - Protective effects of inactive Adar1 protein and mutations reducing cell death in Adar mutant mouse pups
KW  - Adar, RNA, Placenta, Survival
N2  - The AdarE861A mutant encoding catalytically inactive Adar1 RNA editing enzyme is embryonic lethal but embryos survive 2 days longer than embryo with the AdarΔ2-13 null mutant. We made strains to compare rescues in AdarΔ2-13 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 AdarΔ2-13 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.
ER  -

MELICHEROVÁ, Janka; Pavla MUSILOVÁ; Liam KEEGAN a Mary Anne O'CONNELL. \textit{Protective effects of inactive Adar1 protein and mutations reducing cell death in Adar mutant mouse pups}. 2023.

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