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Table 1 Summary of the different murine crosses performed to identify rescue of the Adar1 and Adar2 murine phenotypes, respectively

From: Rewriting the transcriptome: adenosine-to-inosine RNA editing by ADARs

Adar allele

Genetic modifier (gene/protein)

Method

Function/substrate

Outcome at birth

Reference(s)

Adar1 –/– (p110 and p150

   

E11.5–12.0 lethal

[30, 90]

Ifih1 –/– (MDA5)

Mouse cross

Long paired dsRNA

Rescue: majority die by 2 days old

[78]

Mavs –/– (MAVS)

Mouse cross; Crispr cell line

Effector of RIG-I and MDA5

Rescue: majority die by 2 days old; small number survive up to 20 days

[78, 92, 93]

Rnasel –/– (RNase L)

Crispr cell line

Endoribonuclease; cleaves dsRNA

Rescue (cell lines)

[93]

Eif2ak2 –/– (PKR)

Mouse cross

dsRNA-activated serine/threonine kinase

No rescue

[90]

Tmem173 –/– (STING)

Mouse cross

Cytosolic DNA sensor

No rescue

[78]

Ddx58 –/– (RIG-I)

Mouse cross

Short 5′ phos RNA (ds and ss)

No rescue

[78]

Stat1 –/– (STAT1)

Mouse cross

Transcriptional effector of interferon pathway

No rescue; lethal by E15.5

[92]

Ifnar –/– (IFNRα)

Mouse cross

Type I interferon receptor

No rescue; lethal at E14.5–15.5

[78, 92]

Ifnar –/– Ifngr –/– (IFNαR/IFNγR)

Mouse cross

Type I and II interferon receptor

No rescue; lethal at E15.5

[40]

Trp53 –/– (p53)

Mouse cross

Tumor suppressor; can modify cell death

No rescue

Unpublished (J. Hartner and C. Walkley)

Adar1p150 –/– (p150 KO only)

   

E11.5–12.0 lethal

[77]

Mavs –/– (MAVS)

Mouse cross

Effector of RIG-I and MDA5

Rescue: majority survive to 20 days

[78]

Adar1E861A/E861A (editing deficient)

   

E13.5 lethal

[41]

Ifih1 –/– (MDA5)

Mouse cross; cell lines

Long paired dsRNA

Rescue: majority survive normally In vitro cell lines—rescue

[41, 106]

Ifnar –/– Ifngr –/– (IFNαR/IFNγR)

Mouse cross

Type I and II interferon receptor

No rescue; lethal at E15.5

Unpublished (B. Liddicoat and C. Walkley)

Adar2 –/–

   

Early post-natal lethal (~20 days); seizures

[13]

Gria2 R/R (GluA2 R/R)

Mouse cross

GluA2 glutamate receptor

Rescue; adults normal

[13, 89]