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Strain Name:

B6.129X1-Wasf1tm1Jsco/J

Stock Number:

007445

Availability:

Repository-Cryopreserved

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General Terms and Conditions

Genes & Alleles   Wasf1;   Wasf1tm1Jsco;

Product Information

Strain Details

Type JAX® GEMM® Strain - Congenic
Additional information on JAX® GEMM® Strains.
Type JAX® GEMM® Strain - Mutant Strain
Type JAX® GEMM® Strain - Targeted Mutation
Specieslaboratory mouse
Donating Investigator John Scott,   Oregon Health Science University
GenerationN10pN1

Strain Description
Viability of homozygotes is reduced; approximately 20% die within the first week of life. These animals are small in size, have impaired neurite outgrowth, impaired spinogenesis, elevated long-term potentiation (LTP), decreased long-term depression (LTD), and behavioral abnormalities including reduced sensorimotor function, reduced anxiety and impaired learning and memory (both spatial and non-spatial). Some symptoms are similar to those of patients with 3p-syndrome mental retardation. Protein derived from the targeted locus is absent from brain samples as assessed by immunoblot in mice homozygous for this allele.

Strain Development
A targeting vector was designed to replace the 3' end of exon 4 and a segment of intron 5 with a uracil and neomycin selection cassette. An in-frame stop codon at amino acid 175 and a deletion of 95 bp including the splice donor site of exon 4 were created. The construct was electroporated into 129X1/SvJ-derived JSI-1 embryonic stem (ES) cells. Germline chimeric mice were backcrossed to C57BL/6J for a minimum of 10 generations by the donating laboratory.

Mammalian Phenotype Terms assigned by genotype

The following phenotype information may relate to a genetic background differing from this JAX® Mice strain.

Wasf1tm1Jsco/Wasf1tm1Jsco

        involves: 129X1/SvJ * C57BL/6
  • lethality-postnatal
  • postnatal lethality (MGI Ref ID J:81968)
    • homozygous progeny are observed in lower numbers than expected from heterozygous intercrosses
  • growth/size phenotype
  • decreased body weight (MGI Ref ID J:81968)
    • between 2 and 6 weeks, reduced body size of homozygotes compared to littermates is observed, despite no differences in daily food intake; by 7 weeks of age, mice weigh 90% of control littermates
  • behavior/neurological phenotype
  • abnormal object recognition memory (MGI Ref ID J:81968)
    • mice are unable to distinguish between a novel and familiar object, indicating impaired nonspatial learning/memory
  • abnormal spatial learning (MGI Ref ID J:81968)
    • homozygous mice show impaired spatial learning/memory in a hidden platform swim test
  • decreased anxiety-related response (MGI Ref ID J:81968)
    • null mice spend more time in center of open field compared to controls; in elevated zero maze, homozygotes spend 41% of time in open areas compared to 12 or 14% for wild-type or heterozygous mice
  • impaired balance (MGI Ref ID J:81968)
    • on balance beam, mutants travel 198 cm compared to 568 or 439 cm for wild-type or heterozygous littermates
  • impaired coordination (MGI Ref ID J:81968)
    • mice fall off rotating rod with latency of ~43 seconds compared to 114 and 93 seconds for wild-type and heterozygous mice; mice cannot compensate for this with training
  • nervous system phenotype
  • abnormal CNS synaptic transmission (MGI Ref ID J:117303)
    • abnormal NMDA-mediated synaptic currents (MGI Ref ID J:117303)
      • NMDAR to AMPA receptor fEPSP ratio is significantly higher in null neurons
    • abnormal excitatory postsynaptic potential (MGI Ref ID J:117303)
      • hippocampal slices from mutants display a 29% reduction in maximal fEPSPs
    • enhanced long term potentiation (MGI Ref ID J:117303)
      • early phase of LTP is increased relative to wild-type (seen in responses from 0-60 minutes)
      • L-LTP induced by rapid theta bursts results in modest increase in potentiation at 150-180 minutes
    • reduced long term depression (MGI Ref ID J:117303)
      • LTD is reduced relative to wild-type (seen in responses from 0-60 minutes)
  • abnormal neuron morphology (MGI Ref ID J:117303)
    • growth cones of E18 hippocampal neurons appear more 'spiky' and elongated than wild-type growth cones; roundness index of mutant growth cones is 5.3 compared to wild-type score of 4.3
    • in vivo, CA1 hipoocampal and cortical neurons in 10-week old mice show a reduction in dendritic spine density (104 spines/100 um or 99 spines/100 um in wild type hippocampal or cortical (layer 1) neurons compared to 89 spines/100 um or 79.8 spines/100 um in mutant hippocampal or cortical neurons)
  • abnormal neuron physiology (MGI Ref ID J:117303)
    • cultured E18 hippocampal neurons show 60.1% less neurite outgrowth (sum of axonal and dendrite length) than wild-type neurons after 5 days
    • leading edge of growth cone rarely extended to tips of filopodia
    • lamellipodia extend at rate of 6.85 um/minute compared to 5.84 um/minute observed in wild-type cultured neurons, but retraction velocity is similar for both genotypes

Gene & Allele Details

Allele Symbol Wasf1tm1Jsco
Allele Name targeted mutation 1, John D Scott
Common Name(s) wave-;
Mutation Made By John Scott,   Oregon Health Science University
Strain of Origin129X1/SvJ
ES Cell Line NameOther (see notes)
Gene Symbol and Name Wasf1, WASP family 1
Chromosome 10
Gene Common Name(s) AI195380; AI838537; FLJ31482; KIAA0269; MGC109303; SCAR1; Scar; WAVE; WAVE-1; WAVE1; expressed sequence AI195380; expressed sequence AI838537;
General Note JSI-1 ES cells were used.
Molecular Note Exon 4 was replaced with a cassette containing both uracil- and neomycin-resistance genes. The insertion deleted 95 bp, including the splice donor site of exon 4, and introduced a nonsense mutation at codon 175. Normal protein was undetected by Western blot analysis of homozygous mutant brain tissue. [MGI Ref ID J:81968]

Control Information

  Control
   Wild-type from the colony
   000664 C57BL/6J
 
  Considerations for Choosing Controls

Related Strains

Strains carrying other alleles of Wasf1
007446   B6.129X1-Wasf1tm2Jsco/J
View Strains carrying other alleles of Wasf1     (1 strain)

Additional Web Information

Congenic Nomenclature

Research Applications

This mouse can be used to support research in many areas including:

Developmental Biology Research
Postnatal Mortality

Neurobiology Research
Behavioral and Learning Defects
Neurodevelopmental Defects

References

Selected Reference(s)

Soderling SH; Langeberg LK; Soderling JA; Davee SM; Simerly R; Raber J; Scott JD. 2003. Loss of WAVE-1 causes sensorimotor retardation and reduced learning and memory in mice. Proc Natl Acad Sci U S A 100(4):1723-8. [PubMed: 12578964]  [MGI Ref ID J:81968]

Additional References

Price and Supply Information

Strain Name: B6.129X1-Wasf1tm1Jsco/J
Stock Number: 007445

Price Details

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Supply Details

Standard SupplyRepository-Cryopreserved. Must Be Recovered. Please refer to pricing and supply notes for further information.
Supply Notes Cryorecovery - Standard.
The recovery process begins when a signed agreement form is returned to the Customer Service Department after order placement. Although results vary by strain, at least two males and two females (two pairs) will be provided, typically within 15 weeks of our receipt of the signed agreement form. If the first recovery attempt is unsuccessful or only one pair is recovered, a second recovery will be done, extending the delivery time to approximately 25 weeks. At least one member of each pair will be of known genotype and will carry the mutation if it is a mutant strain. Please note that pairs may not reflect the mating scheme utilized by The Jackson Laboratory prior to cryopreservation of the strain. Mating schemes are sometimes modified for successful cryopreservation. Price represents a repository maintenance fee, which includes the cost of recovery of the strain from the cryopreservation resource and the periodic replacement of the frozen embryos used for recovery.

Cryorecovery to establish a Dedicated Supply for greater quantities of mice.
One to two pairs will be recovered to establish a Dedicated Supply of mice. Price by quotation. For more information on Dedicated Supply, please contact JAX® Services: Tel: 1-800-422-6423 or 1-207-288-5845; Email: jaxservices@jax.org.
This strain is included in the Induced Mutant Resource Colony collection.

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Control InformationView Control Information in Strain Details.

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The Jackson Laboratory's Genotype Promise

The Jackson Laboratory has rigorous genetic quality control and mutant gene genotyping programs to ensure the genetic background of JAX® Mice strains as well as the genotypes of strains with identified molecular mutations. JAX® Mice strains are only made available to researchers after meeting our standards. However, the phenotype of each strain may not be fully characterized and/or captured in the strain data sheets. Therefore, we cannot guarantee a strain's phenotype will meet all expectations. To ensure that JAX® Mice will meet the needs of individual research projects or when requesting a strain that is new to your research, we suggest ordering and performing tests on a small number of mice to determine suitability for your particular project.
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