B6.129-Prkaa1tm1Sbj/Orl

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EMMA IDEM:01417
Citation informationRRID:IMSR_EM:01417 

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International strain nameB6.129-Prkaa1tm1Sbj/Orl
Alternative nameAMPKalpha1-knockout
Strain typeTargeted Mutant Strains : Knock-out
Allele/Transgene symbolPrkaa1tm1Sbj
Gene/Transgene symbolPrkaa1

Information from provider

ProviderSophie Vaulont
Provider affiliationINSERMU567, CNRS UMR8401, universite Paris 5, Institut Cochin
Genetic informationA mouse 129-strain genomic library (Stratagene) was screened with a specific mouse AMPK catalytic alpha1-subunit (Prkaa1) 500-bp fragment. One genomic clone encompassing a 14.5-kb genomic fragment was used to generate the targeting construct, which was linearized at an unique XhoI site and used to electroporate embryonic stem (ES) cells (gift from Anne K. Voss, Gottingen), which were cultured on mitomycin-treated embryonic fibroblast feeder layers. DNA from G418-selected clones was analyzed on Southern blot. DNA was EcoRI-digested and hybridized either with a 5'-external probe consisting of a genomic SalI-HincII fragment or with a 3'-external probe consisting of a SacI-SacI genomic fragment. Positive ES cells were injected into blastocysts derived from C57BL/6J mice, and chimeric males were mated to wild-type C57BL/6J females for germ line transmission.
Phenotypic informationHomozygous embryos die in utero on C57BL/6 background but not on a B6 x 129 background. On mixed background, no defect in glucose homoeostasis was observed in AMPK alpha 1 knock-out mice but the weight of different adipose tissue depots is strongly reduced in these mice, suggesting the potential anti-lipolytic role of AMPK in this tissue.
Breeding historyAMPKalpha1(+/-) mice were backcrossed 10 times to C57BL/6J background at the CDTA germ-free animal house in Orleans. At this point no homozygous animals were obtained so it was decided to breed the line with heterozygous animals.
References
  • Knockout of the alpha2 but not alpha1 5'-AMP-activated protein kinase isoform abolishes 5-aminoimidazole-4-carboxamide-1-beta-4-ribofuranosidebut not contraction-induced glucose uptake in skeletal muscle.;Jørgensen Sebastian B, Viollet Benoit, Andreelli Fabrizio, Frøsig Christian, Birk Jesper B, Schjerling Peter, Vaulont Sophie, Richter Erik A, Wojtaszewski Jørgen F P, ;2004;The Journal of biological chemistry;279;1070-9; 14573616
  • Anti-lipolytic action of AMP-activated protein kinase in rodent adipocytes.;Daval Marie, Diot-Dupuy Francine, Bazin Raymond, Hainault Isabelle, Viollet Benoît, Vaulont Sophie, Hajduch Eric, Ferré Pascal, Foufelle Fabienne, ;2005;The Journal of biological chemistry;280;25250-7; 15878856
  • Activation of the AMP-activated kinase by antidiabetes drug metformin stimulates nitric oxide synthesis in vivo by promoting the association of heat shock protein 90 and endothelial nitric oxide synthase.;Davis Bradley J, Xie Zhonglin, Viollet Benoit, Zou Ming-Hui, ;2006;Diabetes;55;496-505; 16443786
Homozygous fertileno
Homozygous viableno
Homozygous matings requiredno

Information from EMMA

Archiving centreCNRS-TAAM – Typing and Archiving of Animal Models, Orléans, France
Animals used for archivingheterozygous C57BL/6J males, wild-type C57BL/6J females
Stage of embryos2-cell

Disease and phenotype information

MGI phenotypes (allele matching)
  • decreased muscle cell glucose uptake / MGI
  • decreased hematocrit / MGI
  • hemolytic anemia / MGI
  • low mean erythrocyte cell number / MGI
  • reticulocytosis / MGI
  • abnormal erythrocyte osmotic lysis / MGI
  • increased spleen weight / MGI
  • abnormal circulating hormone level / MGI
  • decreased mean corpuscular hemoglobin / MGI
  • increased red blood cell distribution width / MGI
MGI phenotypes (gene matching)
  • decreased hematocrit / MGI
  • hemolytic anemia / MGI
  • low mean erythrocyte cell number / MGI
  • reticulocytosis / MGI
  • abnormal erythrocyte osmotic lysis / MGI
  • increased spleen weight / MGI
  • abnormal circulating hormone level / MGI
  • decreased mean corpuscular hemoglobin / MGI
  • increased red blood cell distribution width / MGI
  • decreased muscle cell glucose uptake / MGI

Literature references

  • Knockout of the alpha2 but not alpha1 5'-AMP-activated protein kinase isoform abolishes 5-aminoimidazole-4-carboxamide-1-beta-4-ribofuranosidebut not contraction-induced glucose uptake in skeletal muscle.;Jørgensen Sebastian B, Viollet Benoit, Andreelli Fabrizio, Frøsig Christian, Birk Jesper B, Schjerling Peter, Vaulont Sophie, Richter Erik A, Wojtaszewski Jørgen F P, ;2004;The Journal of biological chemistry;279;1070-9; 14573616
  • Anti-lipolytic action of AMP-activated protein kinase in rodent adipocytes.;Daval Marie, Diot-Dupuy Francine, Bazin Raymond, Hainault Isabelle, Viollet Benoît, Vaulont Sophie, Hajduch Eric, Ferré Pascal, Foufelle Fabienne, ;2005;The Journal of biological chemistry;280;25250-7; 15878856
  • Activation of the AMP-activated kinase by antidiabetes drug metformin stimulates nitric oxide synthesis in vivo by promoting the association of heat shock protein 90 and endothelial nitric oxide synthase.;Davis Bradley J, Xie Zhonglin, Viollet Benoit, Zou Ming-Hui, ;2006;Diabetes;55;496-505; 16443786
  • Susceptibility to ATP depletion of primary proximal tubular cell cultures derived from mice lacking either the α1 or the α2 isoform of the catalytic domain of AMPK.;Lieberthal Wilfred, Tang Meiyi, Zhang Leiqing, Viollet Benoit, Patel Vimal, Levine Jerrold S, ;2013;BMC nephrology;14;251; 24228806
  • Nitric oxide-induced activation of the AMP-activated protein kinase α2 subunit attenuates IκB kinase activity and inflammatory responses in endothelial cells.;Bess Elke, Fisslthaler Beate, Frömel Timo, Fleming Ingrid, ;2011;PloS one;6;e20848; 21673972
  • Endothelial AMP-Activated Kinase α1 Phosphorylates eNOS on Thr495 and Decreases Endothelial NO Formation.;Zippel Nina, Loot Annemarieke E, Stingl Heike, Randriamboavonjy Voahanginirina, Fleming Ingrid, Fisslthaler Beate, ;2018;International journal of molecular sciences;19;; 30217073

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  • Frozen embryos. Delivered in 4 weeks (after paperwork in place). €1740*
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