Description

Strain Information

Type Gene Trap; Mutant Stock; Additional information on Genetically Engineered Mutant Mice. Species laboratory mouse   Donating Investigator Philippe Soriano,   Fred Hutchinson Cancer Research Center

Description
Mice homozygous for this Zfp640-mutant allele are viable and fertile, with abnormalities in palate bone fusion and increased weight gain observed only in males after adolescence. Homozygotes exhibit defects that affect the same cell types and processes as those controlled by the platelet-derived growth factor (PDGF) pathway, including vasculature, kidney, and skeletal defects. Additionally, homozygotes are reported to have low β-galactosidase activity; in situ hybridization or other sensitive methods may be necessary to detect expression of the lacZ-neo reporter fusion gene. These Zfp640-mutant mice may be useful in studying cellular signaling in development and adult mice; specifically receptor tyrosine kinases (RTK; such as Ras, MAP kinase, PI3K and those in the platelet-derived growth factor (PDGF) family) and immediate early genes (IEG) induced shortly after RTK activation.

Development
The retroviral gene-trap vector ROSAFARY (or reverse orientation splice acceptor for array) was designed with a promoter trap module (SAβgeo*pA; encoding a lacZ-neo fusion gene) and an frt-flanked poly-A trap module (PGKhygSD; PGK promoter-driven hygromycin gene with adenoviral splice donor). This construct was electroporated into 129S4/SvJaeSor-Zfp640 AK7.1 embryonic stem (ES) cells. ES cells correctly targeted to the Zfp640 gene were identified and used to generate mutant mice. Homozygous mice were maintained on a C57BL/6 and 129S4/SvJaeSor mixed genetic background prior to arrival at The Jackson Laboratory.

Although current information (Nov 2007) describes that the intron/exon structure of the Zfp640 gene is unknown due to repetitive sequences in this region of mouse Chromosome 13, the ROSAFARY insertion point is reported to be within the first two introns of the disrupted gene; upstream (and within 10 amino acids) of the coding start site.

The ROSAFARY vector inserts a promoterless lacZ-neo reporter fusion gene (which functions as an artificial 3' terminal exon to intercept and terminate transcription from the targeted gene promoter) as well as a poly-A trap (which functions as an artificial 5' terminal exon to initiate transcription from the insertion site). After inserting into an intron of an endogenous gene at a permissive site and in the correct orientation, the promoter trap module and the poly-A trap module can be activated to form fusion transcripts with the 5' or 3' exons.

Control Information

	Control
	101043 B6129SF1/J	(approximate)
	101045 B6129SF2/J	(approximate)
Considerations for Choosing Controls

Phenotype

Phenotype Information

View Mammalian Phenotype Terms

Mammalian Phenotype Terms

      assigned by genotype

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

Zfp640^{Gt(ROSA)81Sor}/Zfp640^{Gt(ROSA)81Sor}

        involves: 129S4/SvJaeSor

• skeleton phenotype
• abnormal skeleton morphology (MGI Ref ID J:117491)
  • abnormal neural crest derived and thoracic skeleton
• abnormal palatine shelf (MGI Ref ID J:117491)
  • 35% of mice have smaller and less extended towards the midline palatine and presphenoid bones
• abnormal presphenoid bone morphology (MGI Ref ID J:117491)
  • 35% of mice have smaller and less extended towards the midline palatine and presphenoid bones
• abnormal sternum morphology (MGI Ref ID J:117491)
  • 20% of mice have sternum defects including asymmetric or additional fusion of ribs and gaps in the sternum
• asymmetric rib-sternum attachment (MGI Ref ID J:117491)
• abnormal vertebrae morphology (MGI Ref ID J:117491)
  • 10% of mice have widened vertebral arches and forked vertebrae
• abnormal vertebral arch morphology (MGI Ref ID J:117491)
  • 10% of mice have widened vertebral arches and forked vertebrae
• increased rib number (MGI Ref ID J:117491)
  • 20% of mice have a 14th pair of ribs
• growth/size phenotype
• increased body weight (MGI Ref ID J:117491)
  • in males following adolescence
• cellular phenotype
• abnormal cell migration (MGI Ref ID J:117491)
  • mouse embryonic fibroblast cells show reduced migration in a scratch test in response to PDGF stimulation
• craniofacial phenotype
• abnormal palate morphology (MGI Ref ID J:117491)
  • irregularities in fusion persist into adulthood
• abnormal palatine shelf (MGI Ref ID J:117491)
  • 35% of mice have smaller and less extended towards the midline palatine and presphenoid bones
• abnormal presphenoid bone morphology (MGI Ref ID J:117491)
  • 35% of mice have smaller and less extended towards the midline palatine and presphenoid bones
• digestive/alimentary phenotype
• abnormal palate morphology (MGI Ref ID J:117491)
  • irregularities in fusion persist into adulthood
• abnormal palatine shelf (MGI Ref ID J:117491)
  • 35% of mice have smaller and less extended towards the midline palatine and presphenoid bones

View Research Applications

Research Applications

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

Cardiovascular Research
Vascular Defects

Cell Biology Research
Signal Transduction

Developmental Biology Research
Craniofacial and Palate Defects
Growth Defects
Internal/Organ Defects (kidney)
Internal/Organ Defects (multiple)
Internal/Organ Defects (vasculature)
Skeletal Defects

Internal/Organ Research
Kidney Defects

Research Tools
lacZ Expression
Cardiovascular Research (endothelial cell marker (lacZ) for neovascularization)
Cell Biology Research
Developmental Biology Research
Internal/Organ Research

Genes & Alleles

Gene & Allele Information

Allele Symbol		Zfp640Gt(ROSA)81Sor
Allele Name		gene trapped 81, Philippe M Soriano
Allele Type		Gene trapped
Common Name(s)		Mzf6d-;
Mutation Made By		Philippe Soriano,   Fred Hutchinson Cancer Research Center
Strain of Origin		129S4/SvJaeSor
ES Cell Line Name		AK7
ES Cell Line Strain		129S4/SvJaeSor
Site of Expression		Homozygotes are reported to have low b-galactosidase activity; in situ hybridization or other sensitive methods may be necessary to detect expression of the lacZ-neo reporter fusion gene.
Gene Symbol and Name		Zfp640, zinc finger protein 640
Chromosome		13
Gene Common Name(s)		Kruppel associated box containing gene; Mzf6d;
Molecular Note		The Rosafary gene trap vector containing a SAbetaGeo pA promoter trap module and a PGKhygSD poly-A trap module was inserted upstream of the coding sequence. [MGI Ref ID J:117491]

Genotyping

Genotyping Information

Genotyping Protocols

Generic Neo Quantitative PCR, QPCR, vers. 1

Helpful Links

Optimizing PCR Protocols

References

References

Selected Reference(s)

Chen WV; Delrow J; Corrin PD; Frazier JP; Soriano P. 2004. Identification and validation of PDGF transcriptional targets by microarray-coupled gene-trap mutagenesis. Nat Genet 36(3):304-12. [PubMed: 14981515]  [MGI Ref ID J:95727]

Schmahl J; Raymond CS; Soriano P. 2007. PDGF signaling specificity is mediated through multiple immediate early genes. Nat Genet 39(1):52-60. [PubMed: 17143286]  [MGI Ref ID J:117491]

Health & husbandry

Health & Colony Maintenance Information

Colony Maintenance

Breeding & Husbandry	When maintaining a live colony, homozygous mice may be bred.

Purchasing information

Pricing, Supply Level & Notes, Controls, General Terms & Conditions

Pricing

Supply Details

Standard Supply

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

Control Information

	Control
	101043 B6129SF1/J	(approximate)
	101045 B6129SF2/J	(approximate)
Considerations for Choosing Controls
USA, Canada and Mexico - Control Pricing Information for Genetically Engineered Mutant Strains.
International - Control Pricing Information for Genetically Engineered Mutant Strains.

General Terms and Conditions

See Terms of Use

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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Ordering and Purchasing Information

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Contact Information
Orders & Technical Support
Tel: 800.422.6423 or 207.288.5845
Fax: 207.288.6150
Technical Support Email Form

Terms of Use

Terms of Use

General Terms and Conditions

For Licensing and Use Restrictions view the link(s) below:
- Use of MICE by companies or for-profit entities requires a license.

Contact information

General inquiries

Contracts Administration

phone:	207-288-6470
fax:	207-288-6655

JAX^® Mice & Services Conditions of Use

“Each recipient institution, including its employees and other researchers under its control (RECIPIENT), of mice or services using mice from The Jackson Laboratory (TJL) agrees that such mice, descendants of those mice derived by inbreeding or crossbreeding, including unmodified derivatives of those mice or their descendants (“MICE”) shall not be: (i) used for any purpose other than the internal research of the RECIPIENT, (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 with respect to MICE. Acceptance of MICE from TJL shall be deemed agreement by RECIPIENT to these conditions, and departure from these conditions requires The Jackson Laboratory’s prior written authorization.”

In case of dissatisfaction for a valid reason and claimed in writing by a purchaser within ninety (90) days of receipt of MICE, products or services, The Jackson Laboratory will, at its option, provide credit or replacement for the MICE or product received or the services provided.

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MICE and biological materials 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 The Jackson Laboratory’s MICE, products and services. In addition, special terms and conditions of sale of certain MICE, products and services may be set forth separately in The Jackson Laboratory 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 The Jackson Laboratory, 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 The Jackson Laboratory, 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 services by The Jackson Laboratory.