B6.129(FVB)-Prkaa2tm1.1Vio/Orl

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EMMA IDEM:01419
Citation informationRRID:IMSR_EM:01419 

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International strain nameB6.129(FVB)-Prkaa2tm1.1Vio/Orl
Alternative nameAMPKalpha2 knockout
Strain typeTargeted Mutant Strains : Knock-out
Allele/Transgene symbolPrkaa2tm1.1Vio
Gene/Transgene symbolPrkaa2

Information from provider

ProviderSophie Vaulont
Provider affiliationINSERMU567, CNRS UMR8401, universite Paris 5, Institut Cochin
Genetic informationPrkaa2 (or AMPK alpha2) genomic clones were isolated from a mouse 129 strain genomic library (Stratagene). The targeting construct was generated by flanking exon C, which encodes the AMPK alpha2 catalytic domain (corresponding to amino acids 189-260), with cre recombinase-specific loxP sites and inserting a PGK promoter-driven neomycin selection cassette flanked by an additional loxP site. The targeting construct was linearized and electroporated into 129/Sv MPI-I embryonic stem cells. Targeted clones were identified by Southern blot analysis of HindIII digested DNA, using a flanking 5' DNA fragment as a hybridization probe, and genotyping analysis. Cells expanded from targeted clones were injected into C57BL/6 blastocysts, and germline-transmitting chimeric animals were mated with C57BL/6 mice. The resulting heterozygous offspring were bred with EIIa-cre recombinase-expressing transgenic deleter mice to produce AMPKalpha2 (+/-) mice.
Phenotypic informationAMPKalpha2 (-/-) mice presented high glucose levels in the fed period and during an oral glucose challenge associated with low insulin plasma levels. However, in isolated AMPKalpha2 (-/-) pancreatic islets, glucose- and L-arginine-stimulated insulin secretion were not affected. AMPKalpha2 (-/-) mice have reduced insulin-stimulated whole-body glucose utilization and muscle glycogen synthesis rates assessed in vivo by the hyperinsulinemic euglycemic clamp technique. We found an increased daily urinary catecholamine excretion in AMPKalpha2 (-/-) mice, suggesting altered function of the autonomic nervous system that could explain both the impaired insulin secretion and insulin sensitivity observed in vivo.
Breeding historyAMPKalpha2(+/-) mice were backcrossed 9 times to C57BL/6J background at the CDTA germ-free animal house in Orleans.
References
  • The AMP-activated protein kinase alpha2 catalytic subunit controls whole-body insulin sensitivity.;Viollet Benoit, Andreelli Fabrizio, Jørgensen Sebastian B, Perrin Christophe, Geloen Alain, Flamez Daisy, Mu James, Lenzner Claudia, Baud Olivier, Bennoun Myriam, Gomas Emmanuel, Nicolas Gaël, Wojtaszewski Jørgen F P, Kahn Axel, Carling David, Schuit Frans C, Birnbaum Morris J, Richter Erik A, Burcelin Rémy, Vaulont Sophie, ;2003;The Journal of clinical investigation;111;91-8; 12511592
  • Cre-mediated germline mosaicism: a method allowing rapid generation of several alleles of a target gene.;Holzenberger M, Lenzner C, Leneuve P, Zaoui R, Hamard G, Vaulont S, Bouc Y L, ;2000;Nucleic acids research;28;E92; 11058142

Information from EMMA

Archiving centreInstitut de Transgenose, INTRAGENE, Orléans, France
Animals used for archivingheterozygous C57BL/6J males, wild-type C57BL/6J females

Disease and phenotype information

IMPC phenotypes (gene matching)
  • increased circulating alanine transaminase level / IMPC
  • enlarged spleen / IMPC
  • increased circulating creatine kinase level / IMPC
  • decreased circulating alkaline phosphatase level / IMPC
  • decreased circulating serum albumin level / IMPC
  • decreased circulating fructosamine level / IMPC
  • increased circulating aspartate transaminase level / IMPC
  • decreased fasting circulating glucose level / IMPC
  • decreased exploration in new environment / IMPC
MGI phenotypes (allele matching)
  • decreased circulating insulin level / MGI
  • abnormal muscle cell glucose uptake / MGI
  • impaired glucose tolerance / MGI
  • decreased glycogen level / MGI
  • increased circulating free fatty acid level / MGI
  • hyperglycemia / MGI
  • abnormal glucose homeostasis / MGI
  • decreased insulin secretion / MGI
  • abnormal sympathetic nervous system physiology / MGI
  • insulin resistance / MGI
  • homeostasis/metabolism phenotype / MGI
  • abnormal glycogen homeostasis / MGI
  • decreased circulating leptin level / MGI
  • abnormal urine catecholamine level / MGI
MGI phenotypes (gene matching)
  • increased circulating free fatty acid level / MGI
  • hyperglycemia / MGI
  • abnormal glucose homeostasis / MGI
  • decreased circulating insulin level / MGI
  • decreased insulin secretion / MGI
  • abnormal muscle cell glucose uptake / MGI
  • abnormal sympathetic nervous system physiology / MGI
  • impaired glucose tolerance / MGI
  • insulin resistance / MGI
  • homeostasis/metabolism phenotype / MGI
  • abnormal glycogen homeostasis / MGI
  • decreased glycogen level / MGI
  • decreased circulating leptin level / MGI
  • abnormal urine catecholamine level / MGI

Literature references

  • The AMP-activated protein kinase alpha2 catalytic subunit controls whole-body insulin sensitivity.;Viollet Benoit, Andreelli Fabrizio, Jørgensen Sebastian B, Perrin Christophe, Geloen Alain, Flamez Daisy, Mu James, Lenzner Claudia, Baud Olivier, Bennoun Myriam, Gomas Emmanuel, Nicolas Gaël, Wojtaszewski Jørgen F P, Kahn Axel, Carling David, Schuit Frans C, Birnbaum Morris J, Richter Erik A, Burcelin Rémy, Vaulont Sophie, ;2003;The Journal of clinical investigation;111;91-8; 12511592
  • Cre-mediated germline mosaicism: a method allowing rapid generation of several alleles of a target gene.;Holzenberger M, Lenzner C, Leneuve P, Zaoui R, Hamard G, Vaulont S, Bouc Y L, ;2000;Nucleic acids research;28;E92; 11058142
  • 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;2059-2075.e10; 30217073
  • Pharmacological inhibition of arachidonate 12-lipoxygenase ameliorates myocardial ischemia-reperfusion injury in multiple species.;Zhang Xiao-Jing, Liu Xiaolan, Hu Manli, Zhao Guo-Jun, Sun Dating, Cheng Xu, Xiang Hui, Huang Yong-Ping, Tian Rui-Feng, Shen Li-Jun, Ma Jun-Peng, Wang Hai-Ping, Tian Song, Gan Shanyu, Xu Haibo, Liao Rufang, Zou Toujun, Ji Yan-Xiao, Zhang Peng, Cai Jingjing, Wang Zhao V, Meng Guannan, Xu Qingbo, Wang Yibin, Ma Xin-Liang, Liu Peter P, Huang Zan, Zhu Lihua, She Zhi-Gang, Zhang Xin, Bai Lan, Yang Hailong, Lu Zhibing, Li Hongliang, ;2021;Cell metabolism;33;102513; 34536344
  • Macrophage Sprouty4 deficiency diminishes sepsis-induced acute lung injury in mice.;Chen Rong, Cao Chen, Liu Huimin, Jiang Wanli, Pan Rui, He He, Ding Ke, Meng Qingtao, ;2022;Redox biology;58;; 36334381

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