Description

Strain Information

Type Gene Trap; Mutant Stock; Mating System Heterozygote x +/+ sibling         (Female x Male) Species laboratory mouse Generation ?+N1F1 (20-DEC-07)   Donating Investigator Philippe Soriano,   Fred Hutchinson Cancer Research Center

Description
Homozygous embryos E11.5 to E18.5 exhibit hemorrhages and microaneurisms. Histological examination of E18.5 homozygous embryos reveals thin blood vessel walls, hemorrhages and lung edema. There are fewer vascular smooth muscle cells (vSMCs) in blood vessels as indicated by immunohistochemistry for desmin and alpha-smooth muscle actin. Skeletal defects are observed in 20% of animals in the sternum and calvarial bones. Homozygotes die a few hours after birth due to difficulty breathing and bruising is visible beneath the skin. Heterozygotes are viable and fertile. No gene product is detected in homozygous embryos aged ED9.5-12.5 or in adult gonad. These Zfand5-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 (SAbgeo*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-derived AK7.1 embryonic stem (ES) cells. ES cells with the ROSAFARY vector correctly targeted to the Zfand5 gene (in the 1st intron) were identified and used to generate mutant mice. Heterozygous mice were maintained on a mixed B6;129 background prior to arrival at The Jackson Laboratory. The mice were then crossed to C57BL/6J (Stock No. 000664) for one generation.

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
	Wild-type from the colony
Considerations for Choosing Controls

Phenotype

Phenotype Information

Mammalian Phenotype Terms assigned by genotype

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

Zfand5^{Gt(ROSA)72Sor}/Zfand5^{Gt(ROSA)72Sor}

        involves: 129S4/SvJaeSor

• lethality-prenatal/perinatal
• neonatal lethality (MGI Ref ID J:117491)
  • mice die within hours of birth
• skeleton phenotype
• abnormal skeleton morphology (MGI Ref ID J:117491)
  • abnormal neural crest derived and thoracic skeleton
• abnormal calvaria morphology (MGI Ref ID J:117491)
  • 20% of mice have reduced calvarial bones at the midline with increases in the gaps between frontal bones
• abnormal frontal bone morphology (MGI Ref ID J:117491)
  • increases in the gaps between frontal 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)
• craniofacial phenotype
• abnormal calvaria morphology (MGI Ref ID J:117491)
  • 20% of mice have reduced calvarial bones at the midline with increases in the gaps between frontal bones
• abnormal frontal bone morphology (MGI Ref ID J:117491)
  • increases in the gaps between frontal bones
• cardiovascular system phenotype
• abnormal vasculature (MGI Ref ID J:117491)
• vascular smooth muscle cell hypoplasia (MGI Ref ID J:117491)
• hemorrhage (MGI Ref ID J:117491)
  • at E18.5
• internal hemorrhage (MGI Ref ID J:117491)
  • at E18.5-E19.5
• respiratory system phenotype
• pulmonary edema (MGI Ref ID J:117491)
  • at E18.5
• respiratory distress (MGI Ref ID J:117491)
  • at birth mice have difficulty breathing
• muscle phenotype
• vascular smooth muscle cell hypoplasia (MGI Ref ID J:117491)
• 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
• homeostasis/metabolism phenotype
• pulmonary edema (MGI Ref ID J:117491)
  • at E18.5

Research Applications

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

Cell Biology Research
Signal Transduction

Developmental Biology Research
Perinatal Lethality (Homozygous)
Skeletal Defects

Endocrine Deficiency Research
Vasculature Defects

Genes & Alleles

Gene & Allele Information

Allele Symbol		Zfand5Gt(ROSA)72Sor
Allele Name		gene trapped 72, Philippe M Soriano
Common Name(s)		Zfand5-;
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
Gene Symbol and Name		Zfand5, zinc finger, AN1-type domain 5
Chromosome		19
Gene Common Name(s)		2310057A04Rik; 5830475F03Rik; AA415485; RIKEN cDNA 2310057A04 gene; RIKEN cDNA 5830475F03 gene; ZA20D2; ZFAND5A; ZNF216; Za20d2; Zfp216; expressed sequence AA415485; zinc finger protein 216; zinc finger, A20 domain containing 2;
Molecular Note		The Rosafary gene trap vector containing a SAbetaGeo pA promoter trap module and a PGKhygSD poly-A trap module was inserted into the first intron of the locus. [MGI Ref ID J:117491]

Genotyping

Genotyping Information

Genotyping Protocols

Zfand5^{Gt(ROSA)72Sor}, STD PCR, vers. 1

Helpful Links

Optimizing PCR Protocols

References

References

Selected Reference(s)

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

Animal Health Reports

Room Number           AX11

Colony Maintenance

Breeding & Husbandry	When maintaining a live colony, these mice can be bred as heterozygotes. Homozygotes die a few hours after birth.
Diet Information	LabDiet® 5K52/5K67

Purchasing information

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

Pricing

Control Information

	Control
	Wild-type from the colony
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

View JAX^® Mice & Services Conditions of Use.

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

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.

---

Ordering and Purchasing Information

      Purchasing Information
      JAX^® Mice Orders
      Surgical Services

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