JAX Mouse Strain Datasheet - 024844

STOCK Ubr4^tm1.2Nkt/MdnJ

Stock No:: 024844 |; p600 flox

Targeted Mutation

Cryo Recovery

Overview

Also Known As: p600 flox

These p600^flox/flox mice may be useful for studying the embryonic expression of p600.

Donating Investigator

Yoshihiro Nakatani, Dana-Farber Cancer Institute

Genetic overview

Genetic Background	Generation

Ubr4^tm1.2Nkt

Allele Type	Gene Symbol	Gene Name
Targeted (Conditional ready (e.g. floxed), No functional change)	Ubr4	ubiquitin protein ligase E3 component n-recognin 4

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Research Applications

Developmental Biology Research
Neurobiology Research
Research Tools

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Base Price

Starting at:

$2,595.00 Domestic price Cryo Recovery

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Details

Detailed Description

These p600^flox/flox mutant mice possess loxP sites flanking exon 1 of the ubiquitin protein ligase E3 component n-recognin 4 (Ubr4) gene. P600 is involved in cytoskeletal organization, membrane morphogenesis, integrin-mediated survival signaling, calcium-calmodulin signaling, and the N-end rule pathway of ubiquitin-proteasome-mediated proteolysis. Embryonic p600 is essential for liver, cardiac, and brain development. Mice that are homozygous for this allele are viable and fertile. When bred to mice that express tissue-specific Cre recombinase, resulting offspring will have exon 1 deleted in the cre-expressing tissues.

For example, when bred to B6.Cg-Tg(Sox2-cre)1Amc/J mice (Stock No. 008454) expressing Cre-recombinase under the Sox2 promoter, resulting mice die by E14.5 due to severe cardiac problems including ventricular septal defects and thin ventricular walls. Brain of the knockout mice displays thinner cortical plate with significant less Tuj1-positive neurons. Starting from E13.5, the animals display enlarged ventricles. The orientation of the mitotic spindle in cortical neural progenitors is randomized in E12.5 animals.

Development

A targeting vector was designed to insert a loxP site followed by a frt-flanked neomycin resistance (neo) cassette upstream of exon 1, and a second loxP site downstream of exon 1 of the ubiquitin protein ligase E3 component n-recognin 4 (Ubr4) gene. The construct was electroporated into 129S6/SvEvTac-derived TC1 embryonic stem (ES) cells. Correctly targeted ES cells were injected into blastocysts and resulting chimeric males were bred with C57BL/6NCrl females. Offspring were bred with B6;SJL-Tg(ACTFLPe)9205Dym/J transgenic mice (Stock No. 003800) to delete the neo cassette, and progeny were crossed to remove the Flp-expressing transgene. The donating investigator reported that these p600^flox/flox mice were bred to C57BL/6NCrl mice for at least 15 generations (See SNP note below). Upon arrival, mice were bred to C57BL/6NJ inbred mice (Stock No. 005304) for at least one generation to establish the colony.

A 32 SNP (single nucleotide polymorphism) panel analysis, with 27 markers covering all 19 chromosomes and the X chromosome, as well as 5 markers that distinguish between the C57BL/6J and C57BL/6N substrains, was performed on the rederived living colony at The Jackson Laboratory Repository. 5 markers on three choromosomes were segregating, suggesting an incomplete backcross.

Control Suggestions

Wild-type from the colony
005304 C57BL/6NJ

Additional Information

Considerations for Choosing Controls

Selected References

Nakaya T; Ishiguro KI; Belzil C; Rietsch AM; Yu Q; Mizuno SI; Bronson RT; Geng Y; Nguyen MD; Akashi K; Sicinski P; Nakatani Y. 2013. p600 Plays Essential Roles in Fetal Development. PLoS One 8(6):e66269. PubMed: 23824717 MGI: J:203460

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Genetics

Ubr4^tm1.2Nkt

Allele Symbol: Ubr4^tm1.2Nkt

Allele Name	targeted mutation 1.2, Yoshihiro Nakatani
Allele Type	Targeted (Conditional ready (e.g. floxed), No functional change)
Allele Synonym(s)
Gene Symbol and Name	Ubr4, ubiquitin protein ligase E3 component n-recognin 4
Gene Synonym(s)	1810009A16Rik; 1810009A16Rik; A930005E13Rik; A930005E13Rik; D930005K06Rik; D930005K06Rik; Gm1032; LOC381562; N28143; RBAF600; RIKEN cDNA 1810009A16 gene; RIKEN cDNA A930005E13 gene; RIKEN cDNA D930005K06 gene; Rbaf600; ZUBR1; Zubr1; Zubr1; expressed sequence N28143; gene model 1032, (NCBI); mKIAA0462; p600; zinc finger, UBR1 type 1
Strain of Origin	129S6/SvEvTac
Chromosome	4
Molecular Note	An FRT-flanked neomycin resistance cassette with a 5' loxP site was inserted upstream of exon 1. An additional loxP site was inserted downstream of exon 1. Flp-mediated recombination removed the neomycin resistance cassette and left exon 1 floxed.

Disease/Phenotype

Disease Terms

Research Areas By Genotype

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

Developmental Biology Research
- Defects in Extracellular Matrix Molecules
- Internal/Organ Defects
  - brain
  - heart
  - liver
Neurobiology Research
- Cre-lox System
  - loxP-flanked Sequences
Research Tools
- Cre-lox System
  - loxP-flanked Sequences
- Developmental Biology Research
  - Cre-lox System

Mammalian Phenotype Terms by Genotype

The following phenotype relates to a compound genotype created using this strain

Genotype: Ubr4^tm1.2Nkt/Ubr4^tm1.2Nkt Tg(Sox2-cre)1Amc/0
involves: 129S6/SvEvTac * C57BL/6 * CBA * SJL

mortality/aging

lethality throughout fetal growth and development, complete penetrance
- despite being present at E12.5 and E13.5, no mice are present at E14.5

cardiovascular system phenotype

abnormal atrioventricular cushion morphology
- immature inferior atrioventricular endocardial cushion at E12

abnormal heart development
- increased ventricle volume at E12.5 and E13.5

abnormal interventricular septum morphology
- immature at E12.5 and E13.5 with a large canal between left and right ventricle

abnormal liver vasculature morphology
- dilated

enlarged liver sinusoidal spaces
- at E12.5

thin ventricular wall

nervous system phenotype

abnormal brain morphology
- area between the ventricles and cephalic mesenchyme tissue is reduced compared to in control mice
- compressed especially in the posterior portion

abnormal fourth ventricle morphology
- mostly closed

abnormal lateral ganglionic eminence morphology
- severe cell death with cavitation in the lateral and medial ganglionic eminences, localized below the forebrain cortex

abnormal medial ganglionic eminence morphology
- severe cell death with cavitation in the lateral and medial ganglionic eminences, localized below the forebrain cortex

decreased brain size
- at E13.5

liver/biliary system phenotype

abnormal liver parenchyma morphology
- less densely packed

abnormal liver vasculature morphology
- dilated

enlarged liver sinusoidal spaces
- at E12.5

liver hypoplasia
- at E12.5

embryo phenotype

embryo phenotype
- mice exhibit normal labyrinth layer structure and blood vessels of the labyrinth layer

embryonic growth retardation
- mild at E12.5

growth/size/body region phenotype

abnormal head morphology
- bulges sticking up from the middle of the head at E12.5 and more evident at E13.5

embryonic growth retardation
- mild at E12.5

cellular phenotype

abnormal cell death
- severe cell death with cavitation in the lateral and medial ganglionic eminences, localized below the forebrain cortex

increased cell proliferation
- in the heart at E13.5 without an increase in apoptosis

References

Nakaya T; Ishiguro KI; Belzil C; Rietsch AM; Yu Q; Mizuno SI; Bronson RT; Geng Y; Nguyen MD; Akashi K; Sicinski P; Nakatani Y. 2013. p600 Plays Essential Roles in Fetal Development. PLoS One 8(6):e66269. PubMed: 23824717 MGI: J:203460

Additional - Ubr4^tm1.2Nkt related

Belzil C; Asada N; Ishiguro K; Nakaya T; Parsons K; Pendolino V; Neumayer G; Mapelli M; Nakatani Y; Sanada K; Nguyen MD. 2014. p600 regulates spindle orientation in apical neural progenitors and contributes to neurogenesis in the developing neocortex. Biol Open 3(6):475-85. PubMed: 24812355 MGI: J:211278

Pricing & Availability

Cryo Recovery

Domestic
International

Live Mouse

Age

Genotype

Price

weeks

Cryorecovery - Pricing

Service	Genotype	Price
	Heterozygous for Ubr4<tm1.2Nkt>

Progeny testing is not required

The average number of mice provided from recovery of our cryopreserved strains is 10. The total number of animals provided, their gender and genotype will vary. We will fulfill your order by providing at least two pair of mice, at least one animal of each pair carrying the mutation of interest. Please inquire if larger numbers of animals with specific genotype and genders are needed. Animals typically ship between 10 and 14 weeks from the date of your order. If a second cryorecovery is needed in order to provide the minimum number of animals, animals will ship within 25 weeks.

The genotypes of animals provided may not reflect the mating scheme utilized by The Jackson Laboratory prior to cryopreservation, or that discussed in the strain description. Please inquire about possible genotypes which will be recovered for this specific strain. The Jackson Laboratory cannot guarantee the reproductive success of mice shipped to your facility. If the mice are lost after the first three days (post-arrival) or do not produce progeny at your facility, a new order and fee will be necessary.

Cryorecovery to establish a Dedicated Supply for greater quantities of mice. Mice recovered can be used to establish a dedicated colony to contractually supply you mice according to your requirements. Price by quotation.

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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 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.

Terms Of Use

Terms of Use

General Terms and Conditions

Questions about Terms of Use

Licensing Information

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Email: TechTran@jax.org

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Also Known As: p600 flox

Donating Investigator

Genetic overview

Research Applications

Base Price

Detailed Description

Development

Control Suggestions

Additional Information

Selected References

Ubr4tm1.2Nkt

Allele Symbol: Ubr4tm1.2Nkt

Disease Terms

Research Areas By Genotype

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

Mammalian Phenotype Terms by Genotype

Genotype: Ubr4tm1.2Nkt/Ubr4tm1.2Nkt Tg(Sox2-cre)1Amc/0involves: 129S6/SvEvTac * C57BL/6 * CBA * SJL

mortality/aging

cardiovascular system phenotype

nervous system phenotype

liver/biliary system phenotype

embryo phenotype

growth/size/body region phenotype

cellular phenotype

References

Additional - Ubr4tm1.2Nkt 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

Progeny testing is not required

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

Ubr4^tm1.2Nkt

Allele Symbol: Ubr4^tm1.2Nkt

Genotype: Ubr4^tm1.2Nkt/Ubr4^tm1.2Nkt Tg(Sox2-cre)1Amc/0
involves: 129S6/SvEvTac * C57BL/6 * CBA * SJL

Additional - Ubr4^tm1.2Nkt related