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

Type Mutant Stock; Targeted Mutation; Additional information on Genetically Engineered and Mutant Mice. Visit our online Nomenclature tutorial. Species laboratory mouse Generation N1F2pN1 Generation Definitions   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

Introduction to Cre-lox technology

Phenotype

Phenotype Information

View Related Disease (OMIM) Terms

Related Disease (OMIM) Terms provided by MGI

- Potential model based on gene homology relationships. Phenotypic similarity to the human disease has not been tested. Deafness, Autosomal Recessive 35; DFNB35   (ESRRB)

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.

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
  • loss of strial margenial cells in mutants is observed; this leads to loss of intraepithelial capillaries   (MGI Ref ID J:124941)
• increased or absent threshold for auditory brainstem response
  • ABR thresholds are variably elevated between 1 and 3 months of age   (MGI Ref ID J:124941)

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

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
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
Hearing Defects

Genes & Alleles

Gene & Allele Information provided by MGI

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; 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. Correctly targeted ES cells were injected into C57BL/6 blastocysts and chimeric males were bred to C57BL/6 (to generate Nr3b2CKO+neo mice). The neomycin selection cassette was excised by crossing to mice constitutively expressing the Flp recombinase (unspecified geneticbackground, see Stock No. 003800), generating this Nr3b2CKO allele with a single FRT site remaining. [MGI Ref ID J:124941]

Genotyping

Genotyping Information

Genotyping Protocols

Esrrb^tm1.1Nat, Standard PCR

Helpful Links

Genotyping resources and troubleshooting

References

References provided by MGI

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]

Additional References

Esrrb^tm1.1Nat related

Onishi A; Peng GH; Poth EM; Lee DA; Chen J; Alexis U; de Melo J; Chen S; Blackshaw S. 2010. The orphan nuclear hormone receptor ERRbeta controls rod photoreceptor survival. Proc Natl Acad Sci U S A 107(25):11579-84. [PubMed: 20534447]  [MGI Ref ID J:161283]

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 maintaining a live colony, homozygous mice may be bred together.

Pricing and Purchasing

Pricing, Supply Level & Notes, Controls

Control Information

	Control
	101043 B6129SF1/J	(approximate)
	101045 B6129SF2/J	(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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