Description

Strain Information

Type Mutant Stock; Targeted Mutation; Additional information on Genetically Engineered Mutant Mice. Mating System Homozygote x Homozygote         (Female x Male) Species laboratory mouse Generation N1+F1 (24-APR-08)   Donating Investigator Jeremy Nathans,   Johns Hopkins University

Description
Mice homozygous for this Nr3b2^CKO allele possess loxP sites flanking exon 2 of the targeted gene and are viable and fertile. When these mutant mice are bred to mice that express Cre recombinase, resulting offspring will have the exon containing the initiator methionine codon and encoding the N-terminal 132 amino acids (including part of the DNA-binding domain) deleted in the cre-expressing tissue(s). Of note, if the conditional Nr3b2^CKO is deleted by Cre recombinase in the placenta and embryo, embryonic lethality will result (placental defect). If the conditional Nr3b2^CKO is deleted by Cre recombinase only in the embryo, the resulting mice exhibit an inner ear defect (decreased endolymph production) resulting in deafness and defective balance. These Nr3b2^CKO mutant mice may be useful in generating conditional mutations to study disorders of hearing and balance, inner ear development (such as endolymph-producing epithelia within the auditory and vestibular divisions), and control of cell fate decisions by nuclear receptors.

When bred to a strain expressing Cre recombinase in the nervous system (see Stock No. 003771 for example), this mutant mouse strain may be useful in studies of endolymph producing epithelial cells.

When bred to a strain expressing Cre recombinase in epiblast derived cells (see Stock No. 004783, 008454 for example), this mutant mouse strain may be useful in studies of endolymph producing epithelial cells.

Development
A targeting vector was designed to place a loxP site 184 bp upstream, as well as a loxP site 123 bp downstream of exon 2 of the targeted gene. An FRT-flanked PGK-neo cassette was also placed just downstream of the 3' loxP site. This construct was electroporated into 129S6/SvEvTac-derived embryonic stem (ES) cells. Correctly targeted ES cells were injected into C57BL/6 blastocysts and chimeric males were bred to C57BL/6. The neomycin selection cassette was excised by crossing to mice constitutively expressing the Flp recombinase (unspecified genetic background, see Stock No. 003800). Mice harboring this Nr3b2^CKO conditional allele (and a single remaining FRT site) were bred together for many generations prior to arrival at The Jackson Laboratory. Upon arrival, mice were bred to C57BL/6J for at least one generation to establish the colony.

Control Information

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

Additional Web Information

Cre-lox Systems

Phenotype

Phenotype Information

View Mammalian Phenotype Terms

Mammalian Phenotype Terms

      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.

Esrrb^tm1.1Nat/Esrrb^tm1.2Nat Tg(Nes-cre)1Kln/0

        involves: 129S6/SvEvTac * C57BL/6 * SJL   (conditional)

• hearing/vestibular/ear phenotype
• absent strial marginal cells (MGI Ref ID J:124941)
  • loss of strial margenial cells in mutants is observed; this leads to loss of intraepithelial capillaries
• decreased brainstem auditory evoked potential (MGI Ref ID J:124941)
  • ABRs are variably elevated between 1 and 3 months of age

Esrrb^tm1.1Nat/Esrrb^tm1.2Nat Tg(Sox2-cre)1Amc/0

        involves: 129S6/SvEvTac * C57BL/6 * CBA * SJL   (conditional)

• behavior/neurological phenotype
• absent startle reflex (MGI Ref ID J:124941)
  • no auditory startle reflex
• circling (MGI Ref ID J:124941)
  • adults spin or run in circles
• head bobbing (MGI Ref ID J:124941)
  • observed beginning at several weeks of age
• hearing/vestibular/ear phenotype
• abnormal scala media morphology (MGI Ref ID J:124941)
  • collapsed at 7 days of age
• small scala media (MGI Ref ID J:124941)
  • reduction in volume seen at 4 days of age
• abnormal semicircular canal (MGI Ref ID J:124941)
  • narrowing of membranous labyrinths of the three semicircular canals is observed in postnatal animals
• abnormal semicircular canal ampulla morphology (MGI Ref ID J:124941)
  • flattening of ampullae is observed postnatally
• absent startle reflex (MGI Ref ID J:124941)
  • no auditory startle reflex
• circling (MGI Ref ID J:124941)
  • adults spin or run in circles
• decreased brainstem auditory evoked potential (MGI Ref ID J:124941)
• decreased endolymph production (MGI Ref ID J:124941)
• head bobbing (MGI Ref ID J:124941)
  • observed beginning at several weeks of age

View Research Applications

Research Applications

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

Internal/Organ Research
Other
Other Organ Defects
X Placental Development

Neurobiology Research
Cre-lox System (loxP-flanked Sequences)
Vestibular and Hearing Defects

Research Tools
Cre-lox System (loxP-flanked Sequences)
Developmental Biology Research (Cre-lox System)
Internal/Organ Research
Neurobiology Research
Sensorineural Research

Sensorineural Research
Vestibular and Hearing Defects

Genes & Alleles

Gene & Allele Information

Allele Symbol		Esrrbtm1.1Nat
Allele Name		targeted mutation 1.1, Jeremy Nathans
Allele Type		Targeted (Floxed/Frt)
Common Name(s)		CKOflp; Nr3b2CKO;
Mutation Made By		Jeremy Nathans,   Johns Hopkins University
Strain of Origin		129S6/SvEvTac
Gene Symbol and Name		Esrrb, estrogen related receptor, beta
Chromosome		12
Gene Common Name(s)		DFNB35; ERR2; ERRb; ERRbeta; ERRbeta-2; ESRL2; Err2; Estrrb; NR3B2; estrogen receptor related 2;
Molecular Note		A targeting vector was designed to place a loxp site 184 bp upstream, as well as a loxP site 123 bp downstream of exon 2 of the targeted gene. An FRT-flanked PGK-neo cassette was also placed just downstream of the 3' loxP site. This construct was electroporated into 129S6/SvEvTac-derived embryonic stem (ES) cells. Correctly targeted ES cells were injected into C57BL/6 blastocysts and chimeric males were bred to C57BL/6 (to generate Nr3b2 mice). The neomycin selection cassette was excised by crossing to mice constitutively expressing the Flp recombinase (unspecified genetic background, see Stock No. 003800), generating this Nr3b2 allele with a single FRT site remaining. [MGI Ref ID J:124941]

Genotyping

Genotyping Information

Genotyping Protocols

Esrrb^tm1.1Nat, STD PCR, vers. 1

Helpful Links

Optimizing PCR Protocols

References

References

Selected Reference(s)

Chen J; Nathans J. 2007. Estrogen-Related Receptor beta/NR3B2 Controls Epithelial Cell Fate and Endolymph Production by the Stria Vascularis. Dev Cell 13(3):325-37. [PubMed: 17765677]  [MGI Ref ID J:124941]

Health & husbandry

Health & Colony Maintenance Information

Animal Health Reports

Room Number           AX12

Colony Maintenance

Breeding & Husbandry	When maintaining a live colony, homozygous mice may be bred together.
Mating System	Homozygote x Homozygote         (Female x Male)
Diet Information	LabDiet® 5K52/5K67

Purchasing information

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

Pricing

Supply Details

Standard Supply

Repository-Live. A collection of over 1000 strains maintained as live colonies. Individual colonies are sized to meet current customer demand. Delivery for orders of 10 mice or less ranges on average from one to eight weeks; mice are generally shipped between four to six weeks of age with a maximum shipping age of ~nine weeks. Colony sizes do not generally support stringent age specifications for large volumes of mice; however custom orders and larger quantities of mice are easily arranged. Estimated ship dates for all orders provided within 48 hours of order placement.

Supply Notes

Usually shipped between four and eight weeks of age. 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
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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

Effective September 26, 2007: License Requirements for Strains using Cre-lox Technology only apply in Canada, see Licenses for Strains using Cre-lox Technology.

For additional 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

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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.