Overview

Also Known As:WAVE-1 KO

Homozygous mutants exhibit morphological and functional defects of the central nervous with symptoms are similar to those of patients with 3p-syndrome mental retardation.

Donating Investigator

John D. Scott, University of Washington

Genetic overview

Genetic Background	Generation

Wasf1^tm1Jsco

Allele Type	Gene Symbol	Gene Name
Targeted (Null/Knockout)	Wasf1	WAS protein family, member 1

View Genetics

Research Applications

Neurobiology Research
Developmental Biology Research

View All Research Applications

Base Price

Starting at:

$2,854.50 Domestic price Cryo Recovery

View Price List

Details

Detailed Description

Viability of Wasf1 KO 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.

Of note, other Wasf1 KO mutations have been used to study the brain's response during addiction to cocaine. These mice exhibit a significant decrease in the preference for cocaine.

Development

A targeting vector was designed to replace the 3' end of exon 4 and a segment of intron 5 of the WAS protein family, member 1 (Wasf1) gene 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 Suggestions

Wild-type from the colony
000664 C57BL/6J

Additional Information

Considerations for Choosing Controls

Selected References

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):1723-8PubMed: 12578964 MGI: J:81968

View All References

Genetics

Wasf1^tm1Jsco

Allele Symbol: Wasf1^tm1Jsco

Allele Name	targeted mutation 1, John D Scott
Allele Type	Targeted (Null/Knockout)
Allele Synonym(s)	wave^-
Gene Symbol and Name	Wasf1, WAS protein family, member 1
Gene Synonym(s)
Strain of Origin	129X1/SvJ
Chromosome	10
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.
Mutations Made By	John Scott, University of Washington

Disease/Phenotype

Disease Terms

Research Areas By Phenotype

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

Neurobiology Research
- Behavioral and Learning Defects
- Neurodevelopmental Defects
Developmental Biology Research
- Postnatal Lethality

Mammalian Phenotype Terms by Genotype

The following phenotype information is associated with a similar, but not exact match to this JAX^® Mice strain

Genotype: Wasf1^tm1Jsco/Wasf1^tm1Jsco
involves: 129X1/SvJ * C57BL/6

behavior/neurological phenotype

abnormal object recognition memory
- mice are unable to distinguish between a novel and familiar object, indicating impaired nonspatial learning/memory

abnormal spatial learning
- homozygous mice show impaired spatial learning/memory in a hidden platform swim test

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

impaired balance
- on balance beam, mutants travel 198 cm compared to 568 or 439 cm for wild-type or heterozygous littermates

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

growth/size/body region 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

mortality/aging

postnatal lethality
- homozygous progeny are observed in lower numbers than expected from heterozygous intercrosses

nervous system phenotype

abnormal CNS synaptic transmission

abnormal excitatory postsynaptic potential
- hippocampal slices from mutants display a 29% reduction in maximal fEPSPs

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
- in mutant hippocampal or cortical neurons)
- 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
- cultured E18 hippocampal neurons show 60.1% less neurite outgrowth (sum of axonal and dendrite length) than wild-type neurons after 5 days
- 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
- leading edge of growth cone rarely extended to tips of filopodia

abnormal NMDA-mediated synaptic currents
- NMDAR to AMPA receptor fEPSP ratio is significantly higher in null neurons

enhanced long term potentiation
- 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
- LTD is reduced relative to wild-type (seen in responses from 0-60 minutes)

References

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):1723-8PubMed: 12578964 MGI: J:81968

Additional - Wasf1^tm1Jsco related

Technical Support

CONTACT TECHNICAL SUPPORT

Genotyping Protocols
- Standard PCR:Wasf1
- Genotyping resources and troubleshooting
Breeding Considerations

When maintained as a live colony, heterozygotes may be bred with wildtype or C57BL/6J mice.
- Additional Breeding and Husbandry Support
Citation
When using the WAVE-1 KO mouse strain in a publication, please cite the originating article(s) and include JAX stock #007445 in your Materials and Methods section.

Animal Health Reports

Facility Barrier Level Descriptions

Production of mice from cryopreserved embryos or sperm occurs in a maximum barrier room, G200

Pricing & Availability

Cryo Recovery

Domestic
International

Live Mouse

Age

Genotype

Price

weeks

Cryorecovery - Pricing

Service/Product	Description	Price
	Heterozygous or Wild-type for Wasf1<tm1Jsco>

Related Products and Services

Frozen Mouse Embryo	B6.129X1-Wasf1<tm1Jsco>/J	$2595.00
Frozen Mouse Embryo	B6.129X1-Wasf1<tm1Jsco>/J	$2595.00
Frozen Mouse Embryo	B6.129X1-Wasf1<tm1Jsco>/J	$3373.50
Frozen Mouse Embryo	B6.129X1-Wasf1<tm1Jsco>/J	$3373.50

Payment Terms and Conditions

Terms are granted by individual review and stated on the customer invoice(s) and account statement. These transactions are payable in U.S. currency within the granted terms. Payment for services, products, shipping containers, and shipping costs that are rendered are expected within the payment terms indicated on the invoice or stated by contract. Invoices and account balances in arrears of stated terms may result in The Jackson Laboratory pursuing collection activities including but not limited to outside agencies and court filings.

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. We do not guarantee breeding performance and therefore suggest that investigators order more than one breeding pair to avoid delays in their research.

Terms Of Use

General Terms and Conditions

Questions about Terms of Use

Licensing Information

Phone: 207-288-6470

Email: TechTran@jax.org

JAX® Mice, Products & Services Conditions of Use

"MICE" means mouse strains, their progeny derived by inbreeding or crossbreeding, unmodified derivatives from mouse strains or their progeny supplied by The Jackson Laboratory ("JACKSON"). "PRODUCT(S)" means biological materials supplied by JACKSON, and their derivatives. "SERVICES" means projects conducted by JACKSON for other parties that may include but are not limited to the use of MICE or PRODUCTS. "RECIPIENT" means each recipient of MICE, PRODUCTS, or SERVICES provided by JACKSON including each institution, its employees and other researchers under its control. MICE or PRODUCTS shall not be: (i) used for any purpose other than internal research, (ii) sold or otherwise provided to any third party for any use, or (iii) provided to any agent or other third party to provide breeding or other services. Acceptance of MICE, PRODUCTS or SERVICES from JACKSON shall be deemed as agreement by RECIPIENT to these conditions, and departure from these conditions requires JACKSON’s prior written authorization.

No Warranty

MICE, PRODUCTS AND SERVICES ARE PROVIDED "AS IS". JACKSON EXTENDS NO WARRANTIES OF ANY KIND, EITHER EXPRESS, IMPLIED, OR STATUTORY, WITH RESPECT TO MICE, PRODUCTS OR SERVICES, INCLUDING ANY IMPLIED WARRANTY OF MERCHANTABILITY OR FITNESS FOR A PARTICULAR PURPOSE, OR ANY WARRANTY OF NON-INFRINGEMENT OF ANY PATENT, TRADEMARK, OR OTHER INTELLECTUAL PROPERTY RIGHTS.

Credit for PRODUCTS or SERVICES

In case of dissatisfaction for a valid reason and claimed in writing by a purchaser within ninety (90) days of receipt of, PRODUCTS or SERVICES, JACKSON will, at its option, provide credit or replacement for the PRODUCT received or the SERVICES provided; JACKSON makes no other representations and this shall be the exclusive remedy of the purchaser. Please note specific policy for live mice.

Animal Care and Use for SERVICES

Consistent with the requirement for a written understanding regarding animal care and use, the JACKSON Animal Care and Use Committee will review the animal care and use protocol(s) associated with any SERVICES to be performed at JACKSON, and JACKSON shall have ultimate responsibility and authority for the care of animals while on site or in JACKSON custody.

No Liability

In no event shall JACKSON, its trustees, directors, officers, employees, and affiliates be liable for any causes of action or damages, including any direct, indirect, special, or consequential damages, arising out of the provision of MICE, PRODUCTS, or SERVICES, including economic damage or injury to property and lost profits, and including any damage arising from acts or negligence on the part of JACKSON, its agents or employees. Unless prohibited by law, in purchasing or receiving MICE, PRODUCTS, or SERVICES from JACKSON, purchaser or recipient, or any party claiming by or through them, expressly releases and discharges JACKSON from all such causes of action or damages, and further agrees to defend and indemnify JACKSON from any costs or damages arising out of any third party claims.

MICE, PRODUCTS or SERVICES are to be used in a safe manner and in accordance with all applicable governmental rules and regulations.

The foregoing represents the General Terms and Conditions applicable to JACKSON’s MICE, PRODUCTS or SERVICES. In addition, special terms and conditions of sale of certain MICE, PRODUCTS, or SERVICES may be set forth separately in JACKSON web pages, catalogs, price lists, contracts, and/or other documents, and these special terms and conditions shall also govern the sale of these MICE, PRODUCTS and SERVICES by JACKSON, and by its licensees and distributors.

Acceptance of delivery of MICE, PRODUCTS or SERVICES shall be deemed agreement to these terms and conditions. No purchase order or other document transmitted by purchaser or recipient that may modify the terms and conditions hereof, shall be in any way binding on JACKSON, and instead the terms and conditions set forth herein, including any special terms and conditions set forth separately, shall govern the sale of MICE, PRODUCTS or SERVICES by JACKSON.

Also Known As:WAVE-1 KO

Donating Investigator

Genetic overview

Research Applications

Base Price

Detailed Description

Development

Control Suggestions

Additional Information

Selected References

Wasf1tm1Jsco

Allele Symbol: Wasf1tm1Jsco

Disease Terms

Research Areas By Phenotype

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

Mammalian Phenotype Terms by Genotype

Genotype: Wasf1tm1Jsco/Wasf1tm1Jscoinvolves: 129X1/SvJ * C57BL/6

behavior/neurological phenotype

growth/size/body region phenotype

mortality/aging

nervous system phenotype

References

Additional - Wasf1tm1Jsco related

Genotyping Protocols

Breeding Considerations

Citation

Animal Health Reports

Production of mice from cryopreserved embryos or sperm occurs in a maximum barrier room, G200

Live Mouse

Cryorecovery - Pricing

Related Products and Services

Payment Terms and Conditions

The Jackson Laboratory's Genotype Promise

Terms Of Use

Licensing Information

JAX® Mice, Products & Services Conditions of Use

No Warranty

Credit for PRODUCTS or SERVICES

Animal Care and Use for SERVICES

No Liability

Wasf1^tm1Jsco

Allele Symbol: Wasf1^tm1Jsco

Genotype: Wasf1^tm1Jsco/Wasf1^tm1Jsco
involves: 129X1/SvJ * C57BL/6

Additional - Wasf1^tm1Jsco related