Description

The genotypes of the animals provided may not reflect those discussed in the strain description or the mating scheme utilized by The Jackson Laboratory prior to cryopreservation. Please inquire for possible genotypes for this specific strain.

Strain Information

Type Congenic; Mutant Strain; Targeted Mutation; Additional information on Genetically Engineered and Mutant Mice. Visit our online Nomenclature tutorial. Additional information on Congenic nomenclature. Species laboratory mouse Generation N10pN1 Generation Definitions   Donating Investigator John Scott,   Oregon Health Science University

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.

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.

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)

Phenotype

Phenotype Information

View Mammalian Phenotype Terms

Mammalian Phenotype Terms provided by MGI

      assigned by genotype

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

Wasf1^tm1Jsco/Wasf1^tm1Jsco

        involves: 129X1/SvJ * C57BL/6

• mortality/aging
• postnatal lethality
  • homozygous progeny are observed in lower numbers than expected from heterozygous intercrosses   (MGI Ref ID J:81968)
• growth/size phenotype
• decreased body weight
  • 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   (MGI Ref ID J:81968)
• behavior/neurological phenotype
• abnormal object recognition memory
  • mice are unable to distinguish between a novel and familiar object, indicating impaired nonspatial learning/memory   (MGI Ref ID J:81968)
• abnormal spatial learning
  • homozygous mice show impaired spatial learning/memory in a hidden platform swim test   (MGI Ref ID J:81968)
• decreased anxiety-related response
  • 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   (MGI Ref ID J:81968)
• impaired balance
  • on balance beam, mutants travel 198 cm compared to 568 or 439 cm for wild-type or heterozygous littermates   (MGI Ref ID J:81968)
• impaired coordination
  • 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   (MGI Ref ID J:81968)
• nervous system phenotype
• abnormal CNS synaptic transmission   (MGI Ref ID J:117303)
• • abnormal NMDA-mediated synaptic currents
    • NMDAR to AMPA receptor fEPSP ratio is significantly higher in null neurons   (MGI Ref ID J:117303)
  • abnormal excitatory postsynaptic potential
    • hippocampal slices from mutants display a 29% reduction in maximal fEPSPs   (MGI Ref ID J:117303)
  • enhanced long term potentiation
    • early phase of LTP is increased relative to wild-type (seen in responses from 0-60 minutes)   (MGI Ref ID J:117303)
    • L-LTP induced by rapid theta bursts results in modest increase in potentiation at 150-180 minutes   (MGI Ref ID J:117303)
  • reduced long term depression
    • LTD is reduced relative to wild-type (seen in responses from 0-60 minutes)   (MGI Ref ID J:117303)
• abnormal neuron morphology
  • 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   (MGI Ref ID J:117303)
  • 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)   (MGI Ref ID J:117303)
• abnormal neuron physiology
  • cultured E18 hippocampal neurons show 60.1% less neurite outgrowth (sum of axonal and dendrite length) than wild-type neurons after 5 days   (MGI Ref ID J:117303)
  • leading edge of growth cone rarely extended to tips of filopodia   (MGI Ref ID J:117303)
  • 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   (MGI Ref ID J:117303)

View Research Applications

Research Applications

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

Developmental Biology Research
Postnatal Lethality

Neurobiology Research
Behavioral and Learning Defects
Neurodevelopmental Defects

Genes & Alleles

Gene & Allele Information provided by MGI

Allele Symbol		Wasf1tm1Jsco
Allele Name		targeted mutation 1, John D Scott
Allele Type		Targeted (knock-out)
Common Name(s)		wave-;
Mutation Made By		John Scott,   Oregon Health Science University
Strain of Origin		129X1/SvJ
ES Cell Line Name		Other (see notes)
Gene Symbol and Name		Wasf1, WASP family 1
Chromosome		10
Gene Common Name(s)		AI195380; AI838537; SCAR1; Scar; WAVE; WAVE-1; WAVE1; expressed sequence AI195380; expressed sequence AI838537;
General Note		ES cell line = JSI-1.
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]

Genotyping

Genotyping Information

Helpful Links

Genotyping resources and troubleshooting

References

References provided by MGI

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

Wasf1^tm1Jsco related

Soderling SH; Guire ES; Kaech S; White J; Zhang F; Schutz K; Langeberg LK; Banker G; Raber J; Scott JD. 2007. A WAVE-1 and WRP signaling complex regulates spine density, synaptic plasticity, and memory. J Neurosci 27(2):355-65. [PubMed: 17215396]  [MGI Ref ID J:117303]

Health & husbandry

Health & Colony Maintenance Information

Animal Health Reports

Production of mice from cryopreserved embryos or sperm occurs in a maximum barrier room, RG10/RG30.

Purchasing information

Pricing, Supply Level & Notes, Controls

General Supply Notes

• This strain is included in the Induced Mutant Resource Colony collection.

Control Information

	Control
	Wild-type from the colony
	000664 C57BL/6J
Considerations for Choosing Controls
Control Pricing Information for Genetically Engineered Mutant Strains.

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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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