STOCK Eif2ak4tm1.2Dron Eif2ak2tm1Jcbe/Cnbc

Status

Available to order

EMMA IDEM:09408
International strain nameSTOCK Eif2ak4tm1.2Dron Eif2ak2tm1Jcbe/Cnbc
Alternative nameGCN2KO.PKRKO.DKO_PKR_GCN2 Mixed Background
Strain typeTargeted Mutant Strains : Knock-out
Allele/Transgene symbolEif2ak4tm1.2Dron, Eif2ak2tm1Jcbe
Gene/Transgene symbolEif2ak4, Eif2ak2

Information from provider

ProviderJuanjo Berlanga
Provider affiliationGenome Dynamics and Function, Centro de Biología Molecular Severo Ochoa (CSIC-UAM)
Genetic informationPKR-deficient gene (alpha subunit of eukaryotic initiation factor 2 Kinase-eIF2alpha Kinase) with target disruption of the Catalytic Domain of the double-stranded RNA-dependent protein kinase, PKR (Exon 12-encodes subdomains V and VI). Eif2ak4_GCN2-deficient gene (GCN2 allele constitutively missing exon XII (GCN2)). Exon XII encodes a region of GCN2 that binds ATP, and its deletion eliminates kinase activity.
Phenotypic informationHomozygous:
Effect non tested for both mutations in homozygous together. Effect separately: Mice homozygous for Pkr disruption (Pkr 0/0) develop normally and are fertile with average sized litters. IFN-alpha and -beta induction of transcription is intact, and the mice show normal hematopoiesis. Pkr 0/0 mice show responses to vaccinia and influenza infection comparable to control animals or cells. Catalytic disruption of Pkr is not sufficient to ablate eIF-2alpha phosphorylation. GCN2 homozygous mutant mice exhibit a less aversive response towards imbalanced diet, therefore eIF2 kinase GCN2 has an important role in mediating aversion toward foods with an imbalanced amino acid composition. GCN2-induced eIF2 phosphorylation may promote the aversive response through its effects on translation and transcription in cells of the Anterior Piriform Cortex (APC), in other brain regions, and in other peripheral organs.

Heterozygous:
Effect non tested for both mutation in heterozygous together. Effect separately:Mice heterozygous for Pkr disruption (Pkr P/0) develop normally and are fertile with average sized litters. IFN-alpha and -beta induction of transcription is intact, and the mice show normal hematopoiesis. Pkr 0/0 mice show responses to vaccinia and influenza infection comparable to control animals or cells. Catalytic disruption of Pkr is not sufficient to ablate eIF-2alpha phosphorylation. GCN2 heterozygous mutant mice, exhibit a wild-type aversive response toward foods with an imbalanced amino acid composition.
References
  • The GCN2 kinase biases feeding behavior to maintain amino acid homeostasis in omnivores.;Maurin Anne-Catherine, Jousse Céline, Averous Julien, Parry Laurent, Bruhat Alain, Cherasse Yoan, Zeng Huiqing, Zhang Yuhong, Harding Heather P, Ron David, Fafournoux Pierre, ;2005;Cell metabolism;1;273-7; 16054071
  • Regulated translation initiation controls stress-induced gene expression in mammalian cells.;Harding H P, Novoa I, Zhang Y, Zeng H, Wek R, Schapira M, Ron D, ;2000;Molecular cell;6;1099-108; 11106749
  • Characterization of transgenic mice with targeted disruption of the catalytic domain of the double-stranded RNA-dependent protein kinase, PKR.;Abraham N, Stojdl D F, Duncan P I, Méthot N, Ishii T, Dubé M, Vanderhyden B C, Atkins H L, Gray D A, McBurney M W, Koromilas A E, Brown E G, Sonenberg N, Bell J C, ;1999;The Journal of biological chemistry;274;5953-62; 10026221
Homozygous fertileyes
Homozygous viableyes
Homozygous matings requiredno
Immunocompromisedno

Information from EMMA

Archiving centreCNB-CSIC, Centro Nacional de Biotecnologia, Madrid, Spain
Animals used for archivinghomozygous 129/Sv (synonym: 129Sv), homozygous 129/Sv (synonym: 129Sv)
Stage of embryos2-cell

Disease and phenotype information

Orphanet associated rare diseases, based on orthologous gene matching

IMPC phenotypes (gene matching)
  • increased circulating serum albumin level / IMPC
  • small spleen / IMPC
  • increased circulating calcium level / IMPC
  • abnormal spleen morphology / IMPC
  • increased circulating creatinine level / IMPC
MGI phenotypes (allele matching)
  • neoplasm / MGI
  • cellular phenotype / MGI
  • immune system phenotype / MGI
  • decreased erythroid progenitor cell number / MGI
  • increased susceptibility to viral infection / MGI
  • increased sensitivity to induced cell death / MGI
  • decreased sensitivity to induced cell death / MGI
  • increased sensitivity to induced morbidity/mortality / MGI
  • abnormal contextual conditioning behavior / MGI
  • abnormal long term potentiation / MGI
  • abnormal spatial reference memory / MGI
  • abnormal food preference / MGI
  • abnormal dendritic cell physiology / MGI
  • abnormal cytokine secretion / MGI
MGI phenotypes (gene matching)
  • neoplasm / MGI
  • increased susceptibility to viral infection / MGI
  • increased T cell proliferation / MGI
  • cellular phenotype / MGI
  • immune system phenotype / MGI
  • increased susceptibility to type IV hypersensitivity reaction / MGI
  • abnormal cell physiology / MGI
  • increased interleukin-4 secretion / MGI
  • increased sensitivity to induced cell death / MGI
  • decreased sensitivity to induced cell death / MGI
  • decreased erythroid progenitor cell number / MGI
  • increased sensitivity to induced morbidity/mortality / MGI
  • abnormal eating behavior / MGI
  • abnormal food preference / MGI
  • abnormal contextual conditioning behavior / MGI
  • postnatal growth retardation / MGI
  • increased litter size / MGI
  • decreased litter size / MGI
  • abnormal long term potentiation / MGI
  • abnormal dendritic cell physiology / MGI
  • increased susceptibility to viral infection / MGI
  • abnormal macrophage physiology / MGI
  • increased growth rate / MGI
  • abnormal cytokine secretion / MGI
  • decreased liver weight / MGI
  • maternal effect / MGI
  • decreased skeletal muscle mass / MGI
  • abnormal circulating amino acid level / MGI
  • homeostasis/metabolism phenotype / MGI
  • growth/size/body region phenotype / MGI
  • behavior/neurological phenotype / MGI
  • abnormal spatial reference memory / MGI
  • increased sensitivity to induced morbidity/mortality / MGI
  • increased susceptibility to weight loss / MGI
  • mortality/aging / MGI
  • postnatal lethality, incomplete penetrance / MGI

Literature references

  • The GCN2 kinase biases feeding behavior to maintain amino acid homeostasis in omnivores.;Maurin Anne-Catherine, Jousse Céline, Averous Julien, Parry Laurent, Bruhat Alain, Cherasse Yoan, Zeng Huiqing, Zhang Yuhong, Harding Heather P, Ron David, Fafournoux Pierre, ;2005;Cell metabolism;1;273-7; 16054071
  • Regulated translation initiation controls stress-induced gene expression in mammalian cells.;Harding H P, Novoa I, Zhang Y, Zeng H, Wek R, Schapira M, Ron D, ;2000;Molecular cell;6;1099-108; 11106749
  • Characterization of transgenic mice with targeted disruption of the catalytic domain of the double-stranded RNA-dependent protein kinase, PKR.;Abraham N, Stojdl D F, Duncan P I, Méthot N, Ishii T, Dubé M, Vanderhyden B C, Atkins H L, Gray D A, McBurney M W, Koromilas A E, Brown E G, Sonenberg N, Bell J C, ;1999;The Journal of biological chemistry;274;5953-62; 10026221

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Availabilities

Requesting frozen sperm or embryos is generally advisable wherever possible, in order to minimise the shipment of live mice.

  • Frozen embryos. Delivered in 4 weeks (after paperwork in place). €1740*
  • Rederivation of mice from frozen stock, delivery time available upon request . €3880*

Due to the dynamic nature of our processes strain availability may change at short notice. The local repository manager will advise you in these circumstances.

* In addition users have to cover all the shipping costs (including the cost for returning dry-shippers, where applicable).

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