Strain Detail Sheet

Strain Name:
B6.129-Akap5tm1Gsm/Mmmh
Stock Number:
034326-MU
Citation ID:
RRID:MMRRC_034326-MU

Strain Information

Gene Details

Akap5tm1Gsm
Name: A kinase anchor protein 5; targeted mutation 1, G Stanley Mcknight
Synonyms: AKAP150 delta A, AKAP150delta36, D36
Type: Allele
Species: Mus musculus (mouse)
Chromosome: 12
Alteration at locus: Targeted Mutation
Akap5
Name: A kinase anchor protein 5
Synonyms: LOC238276, AKAP150, 3526401B18Rik
Type: Gene
Species: Mouse
Chromosome: 12
Alteration at locus: Targeted Mutation
NCBI: 238276
HGNC: HGNC:375
Homologene: 15854
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Genetic Alterations
For the Akap5tm1Gsm mice, a stop codon (TAG) was engineered into the gene at the Leu710 position, which truncates the last 36 amino acids from the full-length protein. These 36 amino acids contain the PKA binding region. This was achieved by subcloning a 1.5 kb BglII/SpeI fragment containing the Leu710 codon from the targeting vector. Site-directed mutagenesis was performed with the QuickChange kit from Stratagene using Pfu polymerase with the overlapping oligonucleotides: 5'-CAGTATGAAACACTCTAGATAGAAACAGATCTTC- 3' and 5'- AGATGCTGTTTCTATCTAGAGTGTTTCATACTGTT- 3'. The mutated fragment was sequenced to confirm the desired mutation. This engineered D36 mutation also introduces an XbaI restriction site that was used for genotyping. The D36 targeting vector contained the neo cassette flanked by loxP sites downstream from the Akap5 sequence. Constructs were linearized with ClaI and electroporated into R1 ES cells. Targeted ES clones were selected in G418 and identified by Southern Blot analysis using a 39 external probe. Southern blots detected SacI (S) fragments of 10 kb in wild type, 12.4 kb in KO, and 11 kb in D36 recombinant ES cells.
Genotype Determination
ES Cell Line
R1 derived from (129X1/SvJ x 129S1/Sv)F1-Kitl+

Strain Description

Phenotype
Homozygous: Two lines of Akap5 mutant mice were created: a knockout of Akap5 (KO) and a mutant that lacks the PKA binding domain of Akap5tm1Gsm (D36). PKA was found to be delocalized in both the hippocampus and striatum of KO and D36 mice indicating that other neural AKAPs cannot compensate for the loss of PKA binding to AKAP5. In Akap5tm1Gsm mutant mice, a significant fraction of PKA becomes localized to dendritic shafts and this correlates with increased binding to microtubule associated protein- 2 (MAP2). Electrophysiological and behavioral analysis demonstrated more severe deficits in both synaptic plasticity and operant learning in the D36 mice compared with the complete KO animals. Results indicate that the targeting of calcineurin or other binding partners of AKAP5 in the absence of the balancing kinase, PKA, leads to a disruption of synaptic plasticity and results in learning and memory defects.

Heterozygous: Akap5tm1Gsm mice do not show any apparent phenotype and are viable, healthy and fertile.
Mammalian Phenotype Terms
Allelic Composition: Akap5tm1Gsm/Akap5tm1Gsm (Genetic Background: B6.129-Akap5tm1Gsm )
MeSH Terms
  • A Kinase Anchor Proteins/deficiency
  • A Kinase Anchor Proteins/genetics
  • A Kinase Anchor Proteins/physiology
  • Animals
  • Binding Sites
  • Corpus Striatum
  • Cyclic AMP-Dependent Protein Kinases/metabolism
  • Dendrites/metabolism
  • Dendrites/pathology
  • Electrophysiological Phenomena/genetics
  • Hippocampus
  • Learning Disorders/etiology
  • Learning Disorders/genetics
  • Memory Disorders/etiology
  • Memory Disorders/genetics
  • Mice
  • Mice, Knockout
  • Microtubule-Associated Proteins/metabolism
  • Neuronal Plasticity
  • Protein Binding
  • Signal Transduction
  • A Kinase Anchor Proteins
  • Adaptor Proteins, Signal Transducing/genetics
  • Adaptor Proteins, Signal Transducing/isolation & purification
  • Adaptor Proteins, Signal Transducing/metabolism
  • Adaptor Proteins, Signal Transducing/physiology
  • Amino Acid Sequence
  • Calcium Channels, L-Type/isolation & purification
  • Calcium Channels, L-Type/physiology
  • Cyclic AMP-Dependent Protein Kinases/physiology
  • Cytoskeletal Proteins/isolation & purification
  • Isoproterenol/pharmacology
  • Neurons/physiology
  • Phosphorylation/drug effects
  • Rats
  • Receptors, Adrenergic, beta-2/drug effects
  • Receptors, Adrenergic, beta-2/physiology
  • Serine/physiology
  • Signal Transduction/drug effects
  • Signal Transduction/physiology
  • A Kinase Anchor Proteins/metabolism
  • Aging
  • Calcium/metabolism
  • Hippocampus/metabolism
  • Long-Term Potentiation
  • Male
  • Mice, Inbred C57BL
  • Phosphorylation
  • Receptors, AMPA/metabolism
  • Synapses/metabolism
  • Time Factors
Strain Development
Positive ES cell clones were selected for injection into blastocysts to produce chimeric mice that were then bred to C57BL/6 to obtain germ line transmission. Akap5tm1Gsm F1 offspring were crossed to a line of ROSA26-Cre recombinase expressing mice, which removed the neomycin resistance gene leaving a single loxP site. Both the KO and Akap5tm1Gsm mouse lines were backcrossed to C57BL/6 (Charles River) for at least 8 generations.
Suggested Control Mice

Wildtype littermates

MMRRC Genetic QC

MMRRC Genetic QC Summary
The MMRRC Centers have developed a genetic QC pipeline using MiniMUGA array genotyping to provide additional information on strain backgrounds for MMRRC congenic and inbred strains. For more information on when data may be available, or to request genotyping for a strain of interest, please contact mmrrc@missouri.edu. Older strains may not have this information.

Research Applications

  • Cardiovascular
  • Cell Biology
  • Diabetes/Obesity
  • Metabolism
  • Models for Human Disease
  • Neurobiology
  • Research Tools
  • Sensorineural

Strain Origin

Donor
G. Stanley McKnight, Ph.D., University of Washington
Primary Reference
  • Weisenhaus M, Allen ML, Yang L, Lu Y, Nichols CB, Su T, Hell JW, McKnight GS.Mutations in AKAP5 disrupt dendritic signaling complexes and lead to electrophysiological and behavioral phenotypes in mice. PLoS One. 2010 Apr 23;5(4):e10325. (Medline PMID: 20428246)
  • Hall DD, Davare MA, Shi M, Allen ML, Weisenhaus M, McKnight GS, Hell JW.Critical role of cAMP-dependent protein kinase anchoring to the L-type calcium channel Cav1.2 via A- kinase anchor protein 150 in neurons. Biochemistry. 2007 Feb 13;46(6):1635- 46. Epub 2007 Jan 20. (Medline PMID: 17279627)
  • Lu Y, Allen M, Halt AR, Weisenhaus M, Dallapiazza RF, Hall DD, Usachev YM, McKnight GS, Hell JW.Age-dependent requirement of AKAP150-anchored PKA and GluR2-lacking AMPA receptors in LTP.EMBO J. 2007 Nov 28;26(23):4879-90. (Medline PMID: 17972919)

Colony and Husbandry Information

Special Considerations

Akap5tm1Gsm heterozygote males are backcrossed steadily to 2 female C57BL/6Crl wildtype mice to maintain the colony.

Health Status Report

Colony Surveillance Program and Current Health Reports

Mice recovered from a cryo-archive will have health surveillance performed on recipient females. Health reports will be provided prior to shipment. If you require additional health status information, please email mmrrc@missouri.edu.

Order Request Information

Availability Level

Limited quantities of breeder mice (recovered litter) are available from a cryoarchive; recovered litter usually available to ship in 3 to 4 months.

Cryopreserved material may be available upon request, please inquire to mmrrc@missouri.edu for more information.

Conditions of Distribution

Distribution of this strain requires submission of the MMRRC Conditions of Use (COU). A link to the COU web form will be provided via email after an order has been placed; the form should be completed then or the email forwarded to your institutional official for completion.

The donor or their institution limits the distribution to non-profit institutions only.

Fees

Additional charges may apply for any special requests. Shipping costs are in addition to the basic distribution/resuscitation fees. Information on shipping costs and any additional charges will be provided by the supplying MMRRC facility.

Click button to Request this one strain. (Use the MMRRC Catalog Search to request more than one strain.)
MMRRC Item # Description Distribution Fee / Unit (US $)
*Shipping & Handling not included*		 Units Notes
034326-MU-SPERM Cryo-preserved spermatozoa $437.00 / Non-Profit Aliquot Approximate quantity3
034326-MU-RESUS Litter recovered from cryo-archive $2,624.00 / Non-Profit Litter Recovered litter4; additional fees for any special requests.
Cryopreserved material may be available upon request, please inquire to mmrrc@missouri.edu for more information.

1 The distribution fee covers the expense of rederiving mice from a live mouse; you will receive the resulting litter. The litter will contain at minimum one mutant carrier; the actual number of animals and the gender and genotype ratios will vary. (Typically, multiple breeder pairs can be established from the recovered litter.) Prior to shipment, the MMRRC will provide information about the animals recovered. If you anticipate or find that you need to request specific genotypes, genders or quantities of mice in excess of what is likely from a resuscitated litter, you may discuss available options and pricing with the supplying MMRRC facility.

2 An aliquot contains a sufficient number of embryos (in one or more vials or straws and based on the transfer success rate of the MMRRC facility) to transfer into one to three recipients. The MMRRC makes no guarantee concerning embryo transfer success experienced in the recipient investigator's laboratory. Neither gender nor genotype ratios are guaranteed.

3 An aliquot is one straw or vial with sufficient sperm to recover at least one litter of mice, as per provided protocols, when performed at the MMRRC facility. The MMRRC makes no guarantee concerning the success of these procedures when performed outside the MMRRC facilities.

4 The distribution fee covers the expense of resuscitating mice from the cryo-archive; you will receive the resulting litter. The litter will contain at minimum one mutant carrier; the actual number of animals and the gender and genotype ratios will vary. (Typically, multiple breeder pairs can be established from the recovered litter.) Prior to shipment, the MMRRC will provide information about the animals recovered. If you anticipate or find that you need to request specific genotypes, genders or quantities of mice in excess of what is likely from a resuscitated litter, you may discuss available options and pricing with the supplying MMRRC facility.

To request material from the MMRRC: Please fill out our on-line request form (accessible from the catalog search results page, or click the Request this Strain button in the fees section). If you have questions or need assistance completing this form, you may call Customer Service at (800) 910-2291 (in USA or Canada) or (530) 757-5710 (international calls). Before you call, please have with you: the MMRRC item number, quantity needed, Bill-to and Ship-to contact information.