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

Former Names B6;129-Ubbtm2Nat/J    (Changed: 30-MAY-12 ) Type Mutant Stock; Targeted Mutation; Additional information on Genetically Engineered and Mutant Mice. Visit our online Nomenclature tutorial. Species laboratory mouse Generation F?+F14+F29pN1 Generation Definitions   Donating Investigator Jeremy Nathans,   Johns Hopkins University

Description
A targeted insertion located 2 kb 5' of the Ubb ubiquitin b gene (the integration site of the Z/AP reporter) gives constitutive expression of a nuclear-localized beta-galactosidase/neomycin resistance protein reporter (NLS-beta-geo) in the absence of Cre-mediated recombination. Following cre-mediated recombination, the NLS-beta-geo coding region is excised and a downstream open reading frame is expressed. The downstream open reading frame codes two proteins - Norrin (NDP), and GFP with 6xMyc epitope, but the GFP coding region, which follows an IRES, is expressed at very low levels. After cre-mediated recombination in the retina, ectopic Norrin expressed from this locus can rescue the vascular defect caused by a Norrin null mutation.

For example, when crossed to a strain expressing Cre recombinase in epiblast cells (see Stock No. 008454), this mutant mouse strain may be useful in studies of retinal vascularization.

Development
The following elements were inserted, in order, 2 kb 5' of the Ubb gene using 129-derived ES cells: CMV enhancer/beta-actin promoter, loxP site, nuclear beta-geo, 3 stop transcription sites, loxP site, Norrin (Ndp), IRES, GFP, a 6xmyc epitope, rabbit beta-globin 3' UTR. This strain was maintained on a mixed C57BL/6 and 129 background by the donating laboratory.

Control Information

	Control
	000664 C57BL/6J	(approximate)
Considerations for Choosing Controls

Related Strains

Strains carrying other alleles of Iis1

010590	B6;129-Iis1tm1(CAG-Bgeo,-tdTomato/TEVP,-SV2B/GFP)Nat/J
012587	B6;129-Iis1tm3(CAG-Bgeo,-tdTomato/TEVP,-Dlg4,-GFP)Nat/J

View Strains carrying other alleles of Iis1     (2 strains)

Phenotype

Phenotype Information

View Mammalian Phenotype Terms

Mammalian Phenotype Terms provided by MGI

      assigned by genotype

The following phenotype relates to a compound genotype created using this strain.
Contact JAX^® Services jaxservices@jax.org for customized breeding options.

Iis1^{tm2(CAG-Bgeo,-Ndp,-EGFP)Nat}/Iis1^{tm2(CAG-Bgeo,-Ndp,-EGFP)Nat} Tg(Sox2-cre)1Amc/?

        involves: 129 * C57BL/6 * CBA   (conditional)

• mortality/aging
• complete prenatal lethality
  • mid-gestational lethality   (MGI Ref ID J:154020)
• growth/size phenotype
• embryonic growth retardation
  • growth retardation at E10.5   (MGI Ref ID J:154020)
• cardiovascular system phenotype
• abnormal angiogenesis
  • severely disrupted   (MGI Ref ID J:154020)
• abnormal aorta smooth muscle morphology
  • no visceral smooth muscle associated with the aorta at E9.5   (MGI Ref ID J:154020)
• embryogenesis phenotype
• embryonic growth retardation
  • growth retardation at E10.5   (MGI Ref ID J:154020)
• muscle phenotype
• abnormal aorta smooth muscle morphology
  • no visceral smooth muscle associated with the aorta at E9.5   (MGI Ref ID J:154020)

View Research Applications

Research Applications

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

Research Tools
lacZ Expression
Cardiovascular Research
      Cre-lox System
Cre-lox System
      loxP-flanked Sequences
Fluorescent Proteins

Genes & Alleles

Gene & Allele Information provided by MGI

Allele Symbol		Iis1tm2(CAG-Bgeo,-Ndp,-EGFP)Nat
Allele Name		targeted mutation 2, Jeremy Nathans
Allele Type		Targeted (Floxed/Frt)
Common Name(s)		Ubbtm2Nat; Z/Norrin;
Mutation Made By		Jeremy Nathans,   Johns Hopkins University
Strain of Origin		129
Site of Expression		Cre excision of a nuclear-localized beta-galactosidase/neomycin resistance protein reporter (NLS-beta-geo) results in expression of Norrin (NDP) and GFP in cre-expressing tissues.
Gene Symbol and Name		Iis1, intergenic insertion site 1
Chromosome		11
Molecular Note		A site 5' of the Ubb gene was targeted with a construct composed of a CMV/beta-actin enhancer and promoter (CAG), a floxed beta-geo with three transcription termination sites, then Ndb followed by an IRES-EGFP. Cre mediated excision of the floxed beta-geo construct is expected to result in expression of the Ndb/EGFP cassette. [MGI Ref ID J:154020]

Genotyping

Genotyping Information

Genotyping Protocols

Ubb^tm2Nat, Standard PCR

Helpful Links

Genotyping resources and troubleshooting

References

References provided by MGI

Selected Reference(s)

Ye X; Wang Y; Cahill H; Yu M; Badea TC; Smallwood PM; Peachey NS; Nathans J. 2009. Norrin, frizzled-4, and Lrp5 signaling in endothelial cells controls a genetic program for retinal vascularization. Cell 139(2):285-98. [PubMed: 19837032]  [MGI Ref ID J:154020]

Additional References

Iis1^{tm2(CAG-Bgeo,-Ndp,-EGFP)Nat} related

Wang Y; Rattner A; Zhou Y; Williams J; Smallwood PM; Nathans J. 2012. Norrin/Frizzled4 signaling in retinal vascular development and blood brain barrier plasticity. Cell 151(6):1332-44. [PubMed: 23217714]  [MGI Ref ID J:193332]

Health & husbandry

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.

Health & Colony Maintenance Information

Animal Health Reports

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

Colony Maintenance

Breeding & Husbandry	When maintained as a live colony, heterozygotes may be bred. Homozygotes are unhealthy and infertile.

Pricing and Purchasing

Pricing, Supply Level & Notes, Controls

Control Information

	Control
	000664 C57BL/6J	(approximate)
Considerations for Choosing Controls
Control Pricing Information for Genetically Engineered Mutant Strains.

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.

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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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